Bone morphogenetic proteinsand the induction of periodontal      tissue regeneration          INDIAN DENTAL ACADEMY       ...
Introduction:   Tissue engineering defined as the science of    fabrication of new tissues for replacement and    the reg...
   Substantial knowledge has now been gained    about the molecular signals that determine the    emergence of the comple...
   Urist 1964 made the key discovery that Demineralized    bone matrix when implanted heterotopically in    intramuscular...
Endochondral bone formation in subcutaneous space ( rodent)5–20µg of BMPs/OPs.                www.indiandentalacademy.com
The sequential developmental cascade In  endochondral bone formation;activation and migration of undifferentiated mesenchy...
   The dissociative extraction of the demineralized bone    matrix with agents (urea and guanidinium hydrochloride)    yi...
BMPs/OPs induction of cementogenesis and PDLregeneration:   More than 40 related proteins with BMP/OP-like    sequences a...
Bone induction in implantation of highly purifiedbone-derived bovine (BMPs/OPs)           www.indiandentalacademy.com
   The induction of bone by hOP-1 develops as a mosaic    structure with distinct spatial and temporal patterns of    gen...
   BMPs/OPs are involved in tooth morphogenesis at different    stages of development. During the later developmental    ...
Imuuno-localization of BMP- 3 & OP- 1:             www.indiandentalacademy.com
   The localization of BMP-2 in alveolar bone only and    BMP-3 and OP-1 in all three components of the    periodontium, ...
Periodontal tissue regeneration by naturally derived andrecombinant human BMPs/OPs in the nonhuman primate   To induce th...
www.indiandentalacademy.com
   The newly formed Sharpey’s fibers were inserted    perpendicularly into the newly formed cementum    covered by a thin...
   Synchronous but spatially distinct OP-1 and BMP-2    expression during murine root formation points to    specific fun...
   hOP-1 clearly modulates the expression of the    cementogenic phenotype and the induction of    cementogenesis in both...
Perspectives in periodontal tissue    engineering by BMPs:   The capacity of mammalian BMPs/OPs to initiate a    programm...
Upcoming SlideShare
Loading in …5
×

Bone morphogenetic proteins /certified fixed orthodontic courses by Indian dental academy

1,593 views

Published on

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

Published in: Education
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,593
On SlideShare
0
From Embeds
0
Number of Embeds
25
Actions
Shares
0
Downloads
0
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Bone morphogenetic proteins /certified fixed orthodontic courses by Indian dental academy

  1. 1. Bone morphogenetic proteinsand the induction of periodontal tissue regeneration INDIAN DENTAL ACADEMY Leader in Continuing Dental Education www.indiandentalacademy.com
  2. 2. Introduction: Tissue engineering defined as the science of fabrication of new tissues for replacement and the regeneration of lost or destroyed tissues. The three critical ingredients for optimal tissue engineering are;  Soluble molecular signals,  Responding cells with associated cell-surface receptors, and  Assembly of the extracellular matrix This knowledge can now be applied not only to bone regeneration but also to alveolar bone with associated cementum and periodontal ligament regeneration. www.indiandentalacademy.com
  3. 3.  Substantial knowledge has now been gained about the molecular signals that determine the emergence of the complex tissue morphologies during regeneration of the periodontal tissues. The molecular mechanisms for such regeneration are the osteogenic proteins of the transforming growth factor-β superfamily of which the bone morphogenetic and osteogenic proteins (BMPs/OPs) are a class of powerful inducers of endochondral bone differentiation. Lacroix in 1945 hypothesized that bone contains substances which he named osteogenins, that initiate bone growth and differentiation. www.indiandentalacademy.com
  4. 4.  Urist 1964 made the key discovery that Demineralized bone matrix when implanted heterotopically in intramuscular sites of allogenic rat recipients, induces de novo endochondral bone formation by induction. BMP is the generic name for proteins which are extracted from bone matrix with agents such as 4M guanidine hydrochloride, 6M urea in 0.5M CaCl2 or ethylene glycol in an aqueous/nonaqueous solvent mixture. Reddi and Huggins showed that subcutaneous implantation of Demineralized bone matrix results in de novo local endochondral bone differentiation. www.indiandentalacademy.com
  5. 5. Endochondral bone formation in subcutaneous space ( rodent)5–20µg of BMPs/OPs. www.indiandentalacademy.com
  6. 6. The sequential developmental cascade In endochondral bone formation;activation and migration of undifferentiated mesenchymal cells by chemotaxisanchorage dependent cell attachment to the matrix via fibronectin mitosis and proliferation of responding mesenchymal cells differentiation of chondroblasts and deposition of cartilage mineralization of the cartilage angiogenesis, vascular invasion and chondrolysis differentiation of osteoblasts and bone matrix deposition mineralization of the newly induced bone and www.indiandentalacademy.comdifferentiation of hemopoietic marrow in the newly formed ossicles
  7. 7.  The dissociative extraction of the demineralized bone matrix with agents (urea and guanidinium hydrochloride) yielded an insoluble component mainly type I collagen (insoluble collagenous bone matrix) and a soluble protein extract containing the putative osteogenic proteins. The operational reconstitution of the inactive and insoluble collagenous bone matrix with protein extracts after a single step of gel-filtration chromatography restored the biological activity yielding endochondral bone differentiation by induction after recombining the insoluble with the soluble signals. Endochondral bone induction is the result of the combined action of BMPs/OPs and the complementary substratum that delivers the osteogenic activity of the soluble molecular signal. www.indiandentalacademy.com
  8. 8. BMPs/OPs induction of cementogenesis and PDLregeneration: More than 40 related proteins with BMP/OP-like sequences and activities have been sequenced and cloned. each protein either purified to BMPs and the induction of periodontal tissue regeneration homogeneity from natural sources or cloned and expressed by recombinant DNA technology induces endochondral bone formation, by induction in heterotopic sites of a variety of animal models including adult primates. In addition to bone induction, BMPs/OPs are expressed during early development and organogenesis indicating that BMPs/OPs are related members play critical roles as soluble mediators of epithelial–mesenchymal interactions and inductive events unrelated to bone induction. (Hogan 1996; Nakashima 2003) www.indiandentalacademy.com
  9. 9. Bone induction in implantation of highly purifiedbone-derived bovine (BMPs/OPs) www.indiandentalacademy.com
  10. 10.  The induction of bone by hOP-1 develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the transforming growth factor-β superfamily that singly, synergistically initiate and maintain tissue induction and morphogenesis. The expression of OP-1, type IV collagen, BMP-3 and transforming growth factor-β1 mRNAs by Northern blot analyses showed progressing stages of osteogenic differentiation during the initiation of bone formation by the hOP-1 osteogenic device. (Ripamonti 2005) The continuous high-expression patterns of type IV collagen mRNA indicates the critical role of hOP-1 in the induction of angiogenesis. www.indiandentalacademy.com
  11. 11.  BMPs/OPs are involved in tooth morphogenesis at different stages of development. During the later developmental stages of tooth morphogenesis, the induction of cementogenesis, PDL and alveolar bone differentiation which are regulated by the co-ordinated expression of BMPs/OPs. A systematic analysis of the expression of six different BMPs in tooth morphogenesis has shown that the expression patterns of each BMP is different and there is co-distribution between specific family members. Root morphogenesis is a classical example of epithelial– mesenchymal interactions. The localization of BMP-3 and OP-1 during morphogenesis of the mouse root suggests that these proteins play a role during cementogenesis and the assembly www.indiandentalacademy.com periodontal ligament of a functionally oriented fiber syste. (Thomadakis et al 1999)
  12. 12. Imuuno-localization of BMP- 3 & OP- 1: www.indiandentalacademy.com
  13. 13.  The localization of BMP-2 in alveolar bone only and BMP-3 and OP-1 in all three components of the periodontium, indicates that the morphogenesis of periodontal tissues may involve a composite pattern of co-ordinated expression of different signaling isoforms. The mosaicism of BMP/OP expression during root morphogenesis indicates that optimal therapeutic regeneration and tissue engineering may entail binary combinations of osteogenic gene products based on recapitulation of embryonic development. Amino acid sequence variations in the active C-terminal domain of each morphogenetic protein confer specialized activities to BMP/OP isoforms and this is the molecular basis that determines the structure–activity profile of single BMPs/OPs. www.indiandentalacademy.com
  14. 14. Periodontal tissue regeneration by naturally derived andrecombinant human BMPs/OPs in the nonhuman primate To induce the cascade of bone differentiation, the soluble osteogenic molecular signals of the transforming growth factor-β superfamily must be reconstituted with an insoluble signal or substratum that triggers the bone differentiation cascade. Different BMPs/OPs and combinations of these have been implanted in furcation defects of the mandibular first and second molars of adult baboons, which are delivered by insoluble collagenous bone matrices as a carrier. Naturally derived BMPs/Ops induced cementum, periodontal ligament and alveolar bone regeneration in surgically created class II furcation defects of mandibular molars. www.indiandentalacademy.com
  15. 15. www.indiandentalacademy.com
  16. 16.  The newly formed Sharpey’s fibers were inserted perpendicularly into the newly formed cementum covered by a thin layer of cementoid. The sources of responding cells that initiate cementogenesis and periodontal ligament regeneration are still not well understood. Recent studies have indicated that the periodontal ligament system contains stem cells that have the potential to regenerate cementum and periodontal ligament in vivo (Seo et al 2004). www.indiandentalacademy.com
  17. 17.  Synchronous but spatially distinct OP-1 and BMP-2 expression during murine root formation points to specific functions of OP-1 and BMP-2 in periodontal tissue morphogenesis and thus regeneration in postnatal life. The co-localization findings of OP-1 and BMP-2 during tooth morphogenesis has suggested that co- administration of OP-1 and BMP-2 in recombinant form would result in synergistic tissue morphogenesis as a recapitulation of memory of developmental events in the embryo. hBMP-2 was found to be more osteogenic than cementogenic in both beagle dogs and baboons. www.indiandentalacademy.com
  18. 18.  hOP-1 clearly modulates the expression of the cementogenic phenotype and the induction of cementogenesis in both animal models, and also on root surfaces exposed by disease (Ripamonti 2002). hBMP-6 has also been investigated in a periodontal fenestration defect model in rodents. The study indicated that hBMP-6 induced significantly more new cementum formation as compared to control fenestration defects (Huang et al 2005). hBMP-12 has also become the focus of attention for periodontal regenerative studies. (Wikesjo¨ et al. 2004) www.indiandentalacademy.com
  19. 19. Perspectives in periodontal tissue engineering by BMPs: The capacity of mammalian BMPs/OPs to initiate a programmed cellular cascade that results in the induction of bone is a functionally conserved process utilized in embryonic development, recapitulated in post-fetal osteogenesis and can be re-exploited for the therapeutic initiation of periodontal tissue regeneration. The presence of the structure–activity profile amongst soluble osteogenic molecular signals indicates a therapeutic significance in clinical contexts (Ripamonti 2006). A soluble osteogenic and recombinant molecular signals when combined with an insoluble signal, triggers periodontal tissue regeneration with the induction of cementogenesis and insertion of Sharpey’s fibers. Therfore these signals are essential ingredients to engineer periodontal tissue www.indiandentalacademy.com regeneration (Ripamonti 2002 & 2006).

×