Dental, BMP

1. Samar Nouby
BMP

2. outline
• What is the BMP.
• Importance for.
• Their types.
• Function of BMP
• Deficiency and its problem
• Uses in dental field
• Conclusion.

3. definition
• Bone Morphogenetic Proteins (BMPs) are a
group of signaling molecules that belongs to
the Transforming Growth Factor-β (TGF-β)
superfamily of proteins. Initially discovered
for their ability to induce bone formation.
• Acc to Kessler,etal1996 BMPs are bone-
derived factors capable of inducing ectopic
bone formation.

4. importance
• Many processes in early development are
dependent on BMP signaling for cell growth,
proliferation differentiation and apoptosis,
(Kobayashi.,etal 2005).
• Many organ systems have one or more BMPs
that are critical for development.
• Essential during embryogenesis, most
prominently for mesoderm formation and
cardiac development.

5. importance
• also play important roles in:
maintaining adult tissue homeostasis (Huang.etal.2009) ,
such as
I. The maintenance of joint integrity,
II. Initiation of fracture repair,
III. And vascular remodeling.
• BMPs deserve to be called body
morphogenetic proteins (Wagner.,etal.2010).

6. Types of BMP
• More than 40 known BMPs types :we
recognized abt 15 type categorized into
subgroups based on amino acid or nucleotide
similarity.
A. BMP2/4, BMP5/6/7/8, BMP9/BMP10, and
BMP12/13/14 (GDF5/6/7) are subgroups based
on phylogenetic analysis.
B. Analysis with amino acid (Fig.A, panel a) or
nucleotide( panel b)

7. Function of BMP
• BMP1:
I. induce bone and cartilage development,
II. is a metalloprotease that functions in collagen maturation as a
procollagen C-proteinase,
III. is not part of the TGF-β superfamily (Kessler,etal1996) it is the
prototype of a family of putative proteases.
• BMP3:
I. is a negative regulator of bone density.
• BMP2, 4, 6, 7, and 9 :
I. are the osteogenic BMPs, based on their potent bone-inducing
activity.
II. BMP2 is essential for endochondral bone formation.
III. BMP4 serves to regulate limb development

8. Function of BMP
• BMP7:
I. important for eye development, is also crucial in the kidney.
• BMP8:
I. has a demonstrated role in spermatogenesis,
• BMP12:
I. is needed for seminal vesicle development.
• BMP13:
I. is a strong inhibitor of bone formation.
II. has a modulatory role in the development of the eye.
• BMP15 :
I. associated with ovarian function.

9. deficiency
• Deficiency in BMP production or functionality
usually leads to severe defects or pathologies.
• BMP2, 4 results in embryonic lethality.
• BMP1, BMP7, and BMP11 die shortly
after birth.

12. In dental development
• During the later developmental stages of tooth
morphogenesis, the induction of cementogenesis,
periodontal ligament and alveolar bone
differentiation, is regulated by the co-ordinated
expression of BMPs/OPs family member
(Thesleff.1997) .
• six different types of Bmps expressed during tooth
morphogenesis ( Thesleff.1997).

13. In dental development
• localization of BMP-3 during morphogenesis of
the root play a role during Cementogenesis,
alveolar bone, and assembly of a periodontal
ligament fiber system(in all three components of
the periodontium) (Thesleff.1997 and
Thomadakis.,etal 1999).
• While BMP-2 in alveolar bone only.

14. Uses in our field
• Lohara etal 2004, use BMP-2 to stimulate stem
cells (which are responsible for this regeneration
) differentiate pulp cells into odontoblasts
which stimulated by the morphogenetic signal.
• His conclusion was; BMP2 can direct pulp
progenitor/stem cell differentiation into
odontoblasts and result in dentin formation.

15. • Recombinant human BMPs for accelerating bone
fusion in slow-healing fractures.
• Concentrations promote chemotaxis; concentrations
promote mitogenesis and differentiation.
• BMPs in preclinical studies have the potential for:
I. regeneration of alveolar bone, alveolar ridge
augmentation,
II. cartilage repair in the temporomandibular joint,
III. oral implants,
IV. endodontic treatment,
V. regeneration of periodontal tissues.
Uses in our field

16. In endodontic ttt
• BMPs might have a therapeutic role in
endodontics. HOW?
– Ideal therapy for repairing pulp would be anti-
inflammatory and antibacterial.
– This stimulate proliferation of pulp stem cells and
induce their differentiation into odontoblasts to
enhance healing potential and rapid dentin
formation.

17. In endodontic ttt
– Acc to Nakashima .1994, BMP2 and BMP4 can
induce new dentin.
– Recombinant BMP delivered in a scaffold (type I
collagen)or osteodentin.
– the extracellular matrix scaffolding is a critical
component and a prerequisite to odontoblast
differentiation and tubular dentin formation
– Also dentin repairing appear with BMP-7 type I
collagen matrix (Rutherford.,etal.1993).

18. • There are 3 key elements for denal
tissue regeneration are:
1. signals for morphogenesis,
2. progenitor/stem cells. “include:
cells frm marrow, pulp, PDL-derived
cells”.
• scaffolds of extracellular matrix
components. “collagen, fibronectin and
proteoglycans, hyaluronic acid.
• Synthetic foams, fibers, gels and
membranes ”
• The morphogenetic signaling
families include BMPs, FGFs, Shh
and Wnts.
conclusion

19. conclusion
• Acc to Wang.,etal 2014
– Our tissues depend on BMP signaling for
homeostasis, EX; include fracture repair initiation
and pulmonary vascular remodeling.
– BMP signaling have been determined to be either
the causative agent of human disease, or have been
shown to have a strong association.
– the mechanisms of pathogenesis need to be fully
understood.

20. conclusion
– There are many critical biological questions about
BMP signaling remain unanswered:
What are the signals governing BMP signaling?
How are the distinct biological outcomes of a given BMP
in different cell and tissue types regulated?
 hw the actions of different BMPs exerted on the same
cell or tissue types are coordinated?
As yet, it is unclear how the same set of morphogen
families that specify the shape of teeth also confer the
discrete morphologies of incisors, canines, premolars and
molars.