Bone morphogenetic proteins (BMPs) is the generic name for a family of proteins that can form bone de novo, for which they are considered osteoinductive
Bone Morphogenetic Proteins - Role in Periodontal RegenerationDr.Shraddha Kode
BMP's are the multifunctional growth factors extensively studied throughout the years. It has recently gained a lot of interest as therapeutic agents in periodontal regeneration.
Bone morphogenetic proteins (BMPs) is the generic name for a family of proteins that can form bone de novo, for which they are considered osteoinductive
Bone Morphogenetic Proteins - Role in Periodontal RegenerationDr.Shraddha Kode
BMP's are the multifunctional growth factors extensively studied throughout the years. It has recently gained a lot of interest as therapeutic agents in periodontal regeneration.
Distraction osteogenesis is a method of producing unlimited quantities of living bone directly from a special osteotomy by controlled mechanical distraction. The new bone spontaneously bridges the gap and rapidly remodels to a normal macrostructure for the local bone.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
What is fixation?
Fixation in orthopedics is the process by which an injury is rendered immobile. This may be accomplished by internal fixation, or by external fixation.
What is internal fixation?
Internal fixation is an operation in orthopedics that involves the surgical implementation of implants for the purpose of repairing a bone
What is osteosynthesis?
Osteosynthesis is the reduction and internal fixation of a bone fracture with implantable devices that are usually made of metal. It is a surgical procedure with an open or per cutaneous approach to the fractured bone. Osteosynthesis aims to bring the fractured bone ends together and immobilize the fracture site while healing takes place. In a fracture that is rigidly immobilized the fracture heals by the process of intramembranous ossification
INDICATIONS for internal fixation
History of Fracture Treatment and Development Of Modern Osteosynthesis
In the Preantibiotic era, closed reduction of fractures was understandably the rule for most fractures. However, when closed reduction was insufficient, external fixation appliances served to maintain skeletal units in position, frequently without the need for MMF (Maxillo-mandibular fixation) .Following the development of antibiotics, the open treatment of fractures began to be used on a more frequent basis.
Rigid internal fixation (RIF) is “Any form of fixation applied directly to the bones which is strong enough to permit active use of the skeletal structure during the healing phase and also helps in healing”.
Bone fractures have been treated with various conservative techniques for centuries and it was not until the eighteenth century that internal fixation was first documented.
Icart, a French surgeon in Castres, performed ligature fixation with brass wire on a young man with a humeral fracture.
1886, when Hansmann of Hamburg published a technique using retrievable metal bone plates with transcutaneous screws.
Soon after, a Belgian surgeon, Albin Lambotte, improved these techniques and coined the term internal fixation.
Lambotte developed and manufactured a variety of bone plates and screws and much of his armamentarim remained in use until the 1950s.
In the twentieth century, Sherman improved on Lambotte’s designs and created parallel, threaded, finepitched, self-tapping screws. This hardware was made of corrosion-resistant vanadium steel, which was a strength improvement over silver and ivory fixation materials.
BIOLOGY OF BONE AND BONE HEALING
Bone is a complex and ever-evolving connective tissue and serves multiple purposes. Besides being the main constituent of the human skeletal system, bone is highly metabolically active and essential for the regulation of serum electrolytes—namely, calcium and phosphate.
Marrow cavities are filled with hematopoietic elements necessary to manufacture and maintain blood components and regulate the immune system. Bone is comprised
Bone morphogenetic proteins /certified fixed orthodontic courses by Indian ...Indian dental academy
Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients
State of the art comprehensive training-Faculty of world wide repute &Very affordable
Distraction osteogenesis is a method of producing unlimited quantities of living bone directly from a special osteotomy by controlled mechanical distraction. The new bone spontaneously bridges the gap and rapidly remodels to a normal macrostructure for the local bone.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
What is fixation?
Fixation in orthopedics is the process by which an injury is rendered immobile. This may be accomplished by internal fixation, or by external fixation.
What is internal fixation?
Internal fixation is an operation in orthopedics that involves the surgical implementation of implants for the purpose of repairing a bone
What is osteosynthesis?
Osteosynthesis is the reduction and internal fixation of a bone fracture with implantable devices that are usually made of metal. It is a surgical procedure with an open or per cutaneous approach to the fractured bone. Osteosynthesis aims to bring the fractured bone ends together and immobilize the fracture site while healing takes place. In a fracture that is rigidly immobilized the fracture heals by the process of intramembranous ossification
INDICATIONS for internal fixation
History of Fracture Treatment and Development Of Modern Osteosynthesis
In the Preantibiotic era, closed reduction of fractures was understandably the rule for most fractures. However, when closed reduction was insufficient, external fixation appliances served to maintain skeletal units in position, frequently without the need for MMF (Maxillo-mandibular fixation) .Following the development of antibiotics, the open treatment of fractures began to be used on a more frequent basis.
Rigid internal fixation (RIF) is “Any form of fixation applied directly to the bones which is strong enough to permit active use of the skeletal structure during the healing phase and also helps in healing”.
Bone fractures have been treated with various conservative techniques for centuries and it was not until the eighteenth century that internal fixation was first documented.
Icart, a French surgeon in Castres, performed ligature fixation with brass wire on a young man with a humeral fracture.
1886, when Hansmann of Hamburg published a technique using retrievable metal bone plates with transcutaneous screws.
Soon after, a Belgian surgeon, Albin Lambotte, improved these techniques and coined the term internal fixation.
Lambotte developed and manufactured a variety of bone plates and screws and much of his armamentarim remained in use until the 1950s.
In the twentieth century, Sherman improved on Lambotte’s designs and created parallel, threaded, finepitched, self-tapping screws. This hardware was made of corrosion-resistant vanadium steel, which was a strength improvement over silver and ivory fixation materials.
BIOLOGY OF BONE AND BONE HEALING
Bone is a complex and ever-evolving connective tissue and serves multiple purposes. Besides being the main constituent of the human skeletal system, bone is highly metabolically active and essential for the regulation of serum electrolytes—namely, calcium and phosphate.
Marrow cavities are filled with hematopoietic elements necessary to manufacture and maintain blood components and regulate the immune system. Bone is comprised
Bone morphogenetic proteins /certified fixed orthodontic courses by Indian ...Indian dental academy
Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients
State of the art comprehensive training-Faculty of world wide repute &Very affordable
Development of bone
Microstructure of bone
Composition of bone
Formation of osteoblasts
Mineralisation of bone
Formation of osteoclasts
Resorption of bone
Macrostructure of bone
Volume changes in bone
Bone healing
Bone physiology and calcium homeostasisAbdulla Kamal
Bone is a highly specialized supporting framework of the body, characterized by its rigidity, hardness, and power of regeneration and repair.
It protects the vital organs, provides an environment for marrow ,acts as a mineral reservoir for calcium homeostasis and a reservoir of growth factors and cytokines, and also takes part in acid–base balance.
Bone constantly undergoes modeling (reshaping) during life to help it adapt to changing biomechanical forces, as well as remodeling to remove old, micro-damaged bone and replace it with new, mechanically stronger bone to help preserve bone strength.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Tissue reaction to dentofacial orthopedic appliances /certified fixed orthodo...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
0091-9248678078
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Technical terminologies
Osteogenesis: refers to formation of bone.
Osteoinduction: is the process by which osteogenesis is induced.
Osteoconduction: This term means that bone grows on a surface.
Wilson Hench [1987] has suggested that osteoconduction is the
process by which bone is directed so as to conform to a material’s
surface.
Osseointegration: This was first described by Brånemark and co-
workers [1977]. The term was first defined by Albrektsson et al.
[1981] as direct contact (at the light microscope level) between living
bone and implant
3. Bone morphogenetic proteins (BMPs) are multi-functional growth factors
that belong to the transforming growth factor β (TGF- β) superfamily.
The roles of BMPs in embryonic development and cellular functions in
postnatal and adult animals have been extensively studied in recent years.
BMPs are now considered to constitute a group of pivotal morphogenetic
signals, orchestrating tissue architecture throughout the body (Bleuming
SA et al 2007)
According to kessler et al 1996 BMPs are bone derived factors capable of
inducing ectopic bone formation
4. The ability of devitalized bone, when implanted in an animal, to induce a
cellular response resulting in new bone tissue formation has been known
for decades.
This unique activity was observed and researched extensively by an
orthopedic surgeon, Dr. Marshall Urist.
He subsequently demonstrated that this activity could be extracted from the
organic component of bone, and that a protein or proteins were responsible
for this activity.
He thus named this activity “bone morphogenetic protein.”
5. Implantation of this protein component of bone matrix resulted in
a complex series of cellular events including mesenchymal cell
infiltration, cartilage formation, vascularization, bone formation,
and ultimately remodeling of the new bone tissue along with
population by hematopoietic bone marrow elements.
6. BMPs are of tremendous interest as therapeutic agents for healing
bone fractures, including non-union and in open tibial fracture. Also
used in spinal fusion and reported to prevent osteoporosis.
In dentistry, it is used for augmentation of maxillary sinus floor and
alveolar ridge. BMPs may provide a promising alternative to
traditional grafting procedures.
Its scope further extends in treating periodontal bone defects and in
implant placement along with alloplastic materials, root coverage
procedures and in periodontal regeneration.
8. 1. They act as mitogens on undifferentiated mesenchymal cells and
osteoblast precursors. Structurally they are related to TGF-β super
family.
2. BMP 2-12 singly initiate de novo endochondral bone formation.
3. BMPs induce bone formation where as other growth factors such as
TGF-β and PDGF donot.
4. BMPs have an anabolic effect on periodontal tissue through
stimulation of osteoblastic differentiation in human periodontal
ligament cells.
9. 5. Bone graft materials contain varying amount of BMPs such
as BMP 2-4 and a deficiency of BMP like protein retards
bone cell differentiation and may account for failure of
fracture to heal.
6. Recombinant BMPs have shown to promote bone formation.
7. They induce the expression of osteoblast Phenotype
8. Act as chemoattractants for mesenchymal cells and
monocytes as well as binding to extra cellular matrix type 4
collagen.
11. Advances in biochemical techniques and the advent of biotechnology
eventually allowed the purification and subsequent molecular cloning of
the factors responsible for the osteoinductive activity in bone.
The purification process included removal of the mineral component of
bone with acid, extraction of the active component from the remaining
organic matrix of bone using chaotropic agents, and multiple column
chromatography steps.
12. Using amino acid sequence information from this purified
extract, the genes or cDNAs encoding each of the proteins
were cloned molecularly. Analysis of these clones indicated
that the bone-inductive extract consisted of a family of related
proteins, i.e, the “bone morphogenetic proteins”.
13. The use of demineralized freeze-dried bone allograft (DFDBA) had been the
focus of much attention throughout the past 30 years as one such material
which may be capable of promoting regeneration of the attachment
apparatus.
Becker et al. [1994] examined the inductivity of DFDBA by placing it in
human extraction sites and then comparing it histologically to control sites
grafted with autogenous bone.
They reported that within those sites grafted with DFDBA, the DFDBA
particles exhibited osteoblastic activity.
15. A study by Talwar et al have shown that rapid release of BMPs resulted in
bone formation and slow release promotes cementum formation [King, J.
et al 2011]
By affecting the degradation rate of carrier, its release kinetics could be
altered. Resorbable carrier matrices have an unpredictable degradation
rate.
Regeneration may be limited since earlier resorption leads to premature
obliteration of space. In case of non-resorbable carriers such as
ethacrylate/tetrahydrofurfuryl methacrylate (PEM/THFM), amount and
duration of release can be altered by adjusting the preparation method.
16. They have been observed to have an initial rapid relief followed
by a slow release and resiliency in maintaining the space
necessary for proliferation and differentiation of osteogenic cells.
However they necessitate a second surgery for removal.
Release kinetics could be altered through
1.Chemical method- for example gelatin carrier is altered by cross-
linking with glutraldehyde.
2. Magnetic field,
3. Ultrasound
4. Emission of photons.
18. BMP Functions
BMP1
BMP1 does not belong to the TGF-β family of proteins. It
is a metalloprotease that acts on procollagen I, II, and III.
It is involved in cartilage development.
BMP2
Acts as a disulfide-linked homodimer and induces bone
and cartilage formation. It is a candidate as a retinoid
mediator. Plays a key role in osteoblast differentiation.
BMP3 Induces bone formation. Also called osteogenin
BMP4
Regulates the formation of teeth, limbs and bone from
mesoderm. It also plays a role in fracture repair, epidermis
formation, dorsal-ventral axis formation, and ovarian
follical development.
BMP5 Performs functions in cartilage development.
BMP6
Plays a role in joint integrity in adults. Controls iron
homeostasis via regulation of hepcidin
19. BMP Functions
BMP7
Plays a key role in osteoblast differentiation. It also
induces the production of SMAD1. Also key in renal
development and repair.
BMP8a Involved in bone and cartilage development.
BMP8b Expressed in the hippocampus.
BMP10
May play a role in the trabeculation of the embryonic
heart
BMP11 Controls anterior-posterior patterning
BMP15
May play a role in oocyte and follicular
development.
20. BMPs also play a role in a number of non-osteogenic
developmental processes:
•Neural induction represents the earliest step in the determination of
ectodermal cell fates.
•In vertebrates, BMPs act as signals of epidermal induction (Mun˜oz-
Sanjua´n and Brivanlou, 2002).
• BMP-2 directs the development of neural crest cells into neuronal
phenotypes (Christiansen et al., 2000), while BMP-4 and 7 specifically
induce a sympathetic adrenergic phenotype.
21. •BMPs give direction to somite development by inhibiting the process
of myogenesis.
•Physiological roles of BMPs and BMP receptor signaling in normal
bone formation have been investigated.
•Injection of BMP-2 locally over the surface of calvariae of mice
induces periosteal bone formation on the surface of calvariae without
a prior cartilage phase (Chen et al., 1997).
23. •Bone formation can take place by an intramembraneous (direct) or
endochondral (indirect) process.
•In both mechanisms, the induction of bone and cartilage occurs through
an epithelial - mesenchymal interaction that initiates specific cell
differentiation.
•Depending on the concentration gradient BMPs can attract various types
of cells and can act as chemotactic, mitogenic/or differentiating agent.
•BMPs can induce differentiation of mesenchymal progenitor cells into
various cell types including chondroblasts and osteoblasts.
24. BONE INDUCING PROPERTY OF BMPS
Subcutaneous implantation of demineralized bone matrix leads to
endochondral bone formation similar to embryonic bone development.
The sequential developmental cascade includes
1. Activation and migration of undifferentiated mesenchymal cells by
chemotaxis;
2. anchorage-dependent cell attachment to the matrix via fibronectin;
3. mitosis and proliferation of mesenchymal cells;
4. differentiation of cartilage;
25. 5. mineralization of the cartilage;
6. vascular invasion and chondrolysis;
7. differentiation of osteoblasts and deposition of bone matrix;
8. Mineralization of bone
9. Differentiation of hemopoietic marrow in the newly developed
ossicle.
27. Most of the biological action of BMPs are mediated through the
BMP receptors which initiate signaling from the cell surface
when bind to two distinct type I and II serine/threonine kinase
receptors, required for signal transduction.[Massgue J, et al
1996].
BMP receptors are composed of three parts: a short extracellular
domain, a single membrane-spanning domain, and an
intracellular domain with active serine/threonine region.[Lin
HY,1995]
28. The type II receptor is the primary binding site of the ligand and
upon its activation, phosporylation of type I receptor occurs.
It is the type I receptor (or activin receptor-like kinases) that
determines the nature of biologic response.
32. BMPs can signal through both canonical and non-canonical
pathways. In the canonical signaling pathway, they initiate the
signal transduction cascade by binding to cell surface receptors and
forming a heterotetrameric complex comprised of two dimers of
type I and type II serine/threonine kinase receptors
33.
34. The mechanism of the heterotetrameric signaling complex formation can
vary.
For example, BMP6 and BMP7 interact with type II receptors and recruit
type I receptors, whereas BMP2 and BMP4 preferentially bind type I
receptors and recruit type II receptors. [De Caestecker et al 2004].
35. Upon formation of a heterotetrameric complex, the constitutively
active type II receptor transphosphorylates the type I receptor at a
glycine-serine rich motif known as the GS domain. This activates
the type I receptor and allows phosphorylation of the
immediately downstream substrate proteins known as the
receptor-regulated Smads (R-Smads) at a C-terminal SSXS motif.
36. The R-Smads involved in BMP signaling are Smad1, Smad5, and Smad8
(Smad1/5/8).
Rsmads then associate with the co-mediator Smad (co-Smad) Smad4,
and this complex translocates to the nucleus where it functions as a
transcription factor with coactivators and corepressors to regulate gene
expression.
Inhibitory Smads (I-Smads), Smad6 and Smad7 (Smad6/7), are involved
in feedback inhibition of the signaling pathway.
37. Various non-canonical pathways, including the MAPK
cascade, can also lead to regulation of gene expression.
BMP signaling is modulated extracellularly (e.g., Noggin),
intracellularly (e.g., FKBP12, microRNAs, phosphatases, and
I-Smads), and by co-receptors in the plasma membrane (e.g.,
Endoglin).
38. BMP4, for example, was found to activate TAK-1, a serineethreonine
kinase of the MAPKKK family.
In addition to the MAPK pathway, BMP signaling has been found to affect
PI3K/Akt, P/kc, Rho-GTPases, and others.
The specific pathway that is activated upon ligand-receptor interaction is
thus likely dependent upon the extracellular environment, other cellular
activity.
39.
40. Factors Affecting BMP Activity
SYNERGISTIC EFFECT ANTAGONISTIC EFFECT
LOCAL
FACTORS
Basic fibroblast growth factor
(low dose)
Basic fibroblast growth factor (high
dose) [Hanada K, et al 1997]
Transforming growth factor [Hanada
K, et al 1997]
Prostaglandins (PG E1)[Ono I, et
al 1996]
SYSTEMIC
FACTORS
Glucocorticoids[Mayer H, et al
1996]
Vitamin D[Amedee J, et al
1994]
Beta-estradiol[Takuwa Y, et al
1991]
42. The structures of several human BMPs have been identified, it is
possible to use DNA probes to obtain human complimentary DNA
sequence.
The human cDNA is cloned and spliced into a viral expression vector,
E. coli transfected to become carriers have been used to produce BMPs
in large quantities for preclinical and clinical evaluation. Therefore
rh-BMP (recombinant human – rh) produced provides optimum
capability for clinical applications.
In 2002, The US Food and Drug Administration (FDA) approved
BMP-2 and BMP-7 for use in bone regeneration
43. BMP – delivery systems
Several matrices and delivery systems have been used
and evaluated for their efficacy and biocompatibility as
carrier for BMPs. Three major strategies for growth
factor delivery: gene therapy, cell therapy, and protein
therapy.
44. Gene therapy and stem cell-based therapy represent the major advance,
however, presently are still in their infancy regarding safety and efficacy
in human.[Kimelman N, et al 2007].
Protein therapy, on the other hand, has demonstrated the most practical
promise, mainly incorporating osteoinductive morphogens (BMPs) even
so with some limitations.
It was suggested that the clinical efficacy of rhBMPs will depend upon
the carrier system, for effective delivery of adequate protein
concentrations to the desired site.[Mont MA, et al 2004]
45. •An absorbable collagen sponge (ACS) was the first BMP carrier
technology to be approved by the US Food and Drug Administration
(FDA).
•The absorbable collagen sponge is a bovine type I collagen matrix that
is soak loaded with a BMP solution before surgical implantation.
•The rhBMP/ ACS construct has shown the clinical efficacy for a
number of indications; however, it is vulnerable to tissue compression.
•The collagen matrix retains 65% of the BMPs during initial
impregnation and releases it in two phases an initial phase within hours
of implantation and a second phase that depends on nature and
geometrical characteristics.
48. BMPs play an important role in the process of bone modeling and
remodeling through chemotatic, mitogenic or differentiating mechanism
[Sykaras N, et al 2003].
Histological analysis showed that BMPs, in conjunction with the
collagenous matrix, induced cementum, periodontal ligament, and
alveolar bone regeneration.
Another study reported that partially purified osteogenin, isolated from
human bone matrix, when reconstituted with allogenic freeze dried
deminerlized bone matrix, enhanced new connective tissue attachment,
and alveolar bone regeneration in a root submerged environment in a
series of human biopsies.[Bowers G, et al 1991].
49. A study where rhBMP-2 was used in a prepared periodontal defect in
beagle dogs showed significant regeneration of the periodontal
tissues.[Sigurdsson TJ, et al 1996].
The effect of rhBMP-2 was evaluated in the surgically created critical size,
supra alveolar periodontal defects in mandibular premolar teeth in beagle
dogs which were implanted with rhBMP-2/ ACS at different
concentrations.
50. The ankylotic union was observed in the coronal aspect of supra
alveolar defects.
Given the unique action of BMPs on mineralized tissue formation,
obliteration of periodontal ligament space and ankylosis are a potential
complication for the use of BMPs in the periodontium.
51. The BMP/TGF-b signaling pathway mediates osteoblastic
differentiation and in vivo bone formation
BMP-2 and -7 were reported to the play a role in the differentiation of
periodontal ligament stem cells (PDLSC) and dental follicle stem
cells.
Reparative dentin formation was promoted by BMP-2 and 7. Other
members of the BMP family, such as BMP-7/OP-1 have observed
periodontal regeneration in animal model.
53. Tissue engineering aims to reconstruct lost tissues or organs
and is considered as the ultimate regenerative technique.
With the help of tissue engineering, therapies such as the
production of skin to treat burns, bone grafts, arteries to treat
atherosclerotic vascular disease and cartilage for plastic and
reconstructive surgeries have been achieved.
Tissue engineering is being applied in dentistry for the
regeneration of temporo-mandibular joint, periodontal
ligament, dentin, enamel, pulp and integrated tooth tissues.
54. Tissue engineering has three key features namely
• Cells - that synthesize the matrix essential for the new tissue.
• Scaffolds - that provide the environment for the cells to synthesize
matrix.
• Signaling molecules such as growth factors – that facilitate and promote
this action.
The growth factors that have frequently been applied to tissue engineering
include bone morphogenetic proteins (BMPs), basic fibroblast growth
factor (bFGF or FGF-2), vascular epithelial growth factor and
transforming growth factor-b (TGF-b).
55. BMPS IN SOCKET AUGMENTATION:
BMPS when used in augmentation of socket and maxillary sinus
wall [Boyne PJ et al ,1997] were found to promote soft-tissue
healing, minimize surgery time, reduce potential postsurgical
infection, accelerate cell migration and promotes early bone
formation.
57. Application of BMPs for the osseointegration of Endosseous implant
has been evaluated by some authors [King GN et al in 2002].
Osseo-integration is critical for endosseous implant in which there is
complete union of implant with bone. Sometimes there would be
insufficiency in quality or amount of bone, which is addressed by
using grafts or growth factors.
58. In human trial studies conducted by Howell in 1997 and Cochran et al in
2000 using Recombinant human BMP-2 in collagen sponge carrier, bone
formation at the extracted site was observed, which helped in endosseous
implant placement.
Boyne et al in 1997, observed bone formation in sinus lift procedure using
the same combination and this aided in implant placement .
A feasibility study evaluating rhBMP-2/absorbable collagen sponge for
maxillary sinus floor augmentation
60. Rachmiel et al I 2006, evaluated the effect of rhBMP in distraction
osteogenesis in sheep model. 1.5 mm distraction devices were placed
following alveolar segmental osteotomy in sheep.
5 days later rhBMP was injected. Radiographic analysis showed lifting
of the transported segment and union of the distracted segment, newly
formed bone and the native bone.
Thus BMPs when used in the process of distraction osteogenesis
seemed to minimise the consolidation period, allowing early
placement of implants.
61. BMP implanted at the distraction site, may induce the noncommitted
mesenchymal cells to form cells of osteoblastic or chondroblastic
lineage. Thus to reduce the consolidation phase and improve quality of
bone, BMPs can be used in DO procedure.
62. Limitations...
•Lack of bone induction with BMPs combined with hydroxyapatite alone –
probably as a result of the lack of resorption of hydroxyapatite and the tight
binding affinity between BMPs and hydroxyapatite; moreover,
immunogenecity and risk of disease transmission with the use of
demineralized bone matrix and acidic breakdown products of synthetic
polymers which might prove detrimental to wound healing.
63. •A further complicating factor is that different anatomical sites might
require different kinetics of release for optimal performance.
•A major problem with delivery of growth factor proteins is the
limited bioactivity (half-life) of proteins due to degradation and
difficulty in achieving a controlled release.
65. Despite a lack of complete understanding of BMP cellular
pathways, addition of BMPs remains the growth factor of choice
to induce mesenchymal stem cell differentiation to osteoblasts to
induce bone formation.
However, to date, sufficient human studies with BMPs in
periodontal defects are lacking.
66. Periodontal tissue regeneration entails the induction of periodontal
ligament, cementum, and alveolar bone.
Although, several studies have shown significant regeneration of the
periodontal tissues with the use of BMP, it is important to understand the
biologic processes of periodontal wound healing and the effects of these
biologic processes on BMP activity.
67. Further studies are needed for the development of delivery
systems that have mechanical and surgical properties appropriate
for controlled release of bone morphogenetic proteins and
identifying optimal condition for the use of BMPs for periodontal
regeneration.