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Osteogenesis & OsteolysisOf Alveolar Bone In
Health & DiseaseDr. Sandip Ladani
Guided by,
Dr. Mihir N. ShahDr. Archita Kikani
Dr. Hiral ParikhDr. Niraj Motwani
Guided by,
Dr. Mihir N. ShahDr. Archita Kikani
Dr. Hiral ParikhDr. Niraj Motwani
• Introduction• Development• Bone formation• Regulation of bone formation• Bone resorption• Regulation of bone resorption• Bone Modeling Vs Bone Remodeling• Ageing & Bone• Bone’s Role in Calcium Homeostasis• Alveolar Bone in Disease• Clinical Implication
Contents
Introduction• BONE:
– Bone is a mineralized connective tissue that performs the function of support, protection and locomotion.
• ALVEOLAR PROCESS :
- It is defined as the parts of the maxilla and mandible that support the sockets of the teeth.
Development of Alveolar Process
• Tooth-dependent bony structures.- Schroeder HE, 1991.
• The alveolar process consists of bone which is formed both by cells from – the dental follicle (alveolar bone proper) and – cells which are independent of tooth
development.
Development of the alveolar bone proper
• Late bell stage:– Bony septa and bony bridge start to form.
• Dental Follicle surrounds each tooth germ.• Continued bodily movement.• Major changes in alveolar process.• Height• Cell differentiation from dental follicle
– Fibroblast, cementoblast, osteoblast.• Osteoblast: Alveolar bone proper –Ten Cate, Hoffman
• Size & Shape : Alveolar Bone proper• Rest of bony structure: periosteal bone formation - Schroeder
Remodeling of the alveolar processes during tooth eruption
• The alveolar processes - already grown over the occlusal plane of the developing tooth.
• Gubernacular canal must be widened by osteoclastic bone resorption.• New bone formation at the base of the bony crypt – outward eruption force• Dental Follicle – Key structural component responsible for regulating eruption -
Eskici, Larson EK.• Monocytes containing tartrate-resistant acid phosphatase, an indicator of
lysosyme activity – Osteoclast precursors.• Recent: Factors: - Wise GE
– Colony stimulating factor-1 : recruitment & differentiation of preosteoclasts– Epidermal growth factor : upregulates the production of CSF-1 via its ability to stimulate
the cells of the reduced enamel organ to make interleukin – 1 α
BONE FORMATION
BONE FORMATION
Cellular DifferentiationCellular Differentiation
Stromal stem cellStromal stem cell OsteoblastOsteoblastOsteogenic PathwayOsteogenic Pathway
Controlled by cascade of events involving genetic programming and gene regulation by various hormones, cytokines and growth factors.
Controlled by cascade of events involving genetic programming and gene regulation by various hormones, cytokines and growth factors.
• Collagen type I and Alkaline Phosphatase – characteristic of osteogenic lineage.
• Type II collagen – Lost• Type III collagen – Diminishes progressively.
BONE FORMATION
Osteogenic Master Gene
α2 β
1
Receptor
BONE FORMATION
BONE FORMATION
in vivo
indu
ces
expr
essi
on
subsequent emergence
BONE FORMATION
• Various developmentally regulated genes:• Homeobox genes – hoxa-2, hoxd-13 and hoxa-13, dlx-5, msx-1
and msx-2
• Various developmentally regulated genes:• Homeobox genes – hoxa-2, hoxd-13 and hoxa-13, dlx-5, msx-1
and msx-2
BONE FORMATION
Cbfa1Cbfa1
Functional role in the differentiation of all mineralizing tissue cells. For eg. Odontoblasts, Cementoblasts, Ameloblasts
Complete absence of ossified tissues.
- Komori T et al, 1997
BONE FORMATION
Osteogenic Master Gene
• BMP-2– Upregulates Cbfa1 & Msx-2 leading to osteogenic
differentiation.
• TGF-ß– Increases Cbfa1 – No osteogenic differentiation
Therefore, other factors induced by BMP are necessary for complete expression of the osteoblastic phenotype.
BONE FORMATION
BMP-4InducesInduces
RegulatesRegulates
Potential
factorPotential
factor
BONE FORMATION
REGULATION OF BONE FORMATION
Production of Osteoblastic cells
Activity of Osteoblastic cells
REGULATION OF BONE FORMATION
• Parathyroid Hormone:– Regulates serum calcium levels– Stimulates bone resorption– But also – anabolic effects mediated through
TGF-β and Insulin like Growth Factor-I.
Thus affects Bone remodelingThus affects Bone remodeling
REGULATION OF BONE FORMATION
• Vitamin D3:– Stimulates bone resorption.– Essential for normal bone growth and
mineralization.– Calcium absorption from the intestine.– Strongly stimulates the synthesis of osteocalcin
and osteopontin by osteoblasts.– Suppresses collagen production.
REGULATION OF BONE FORMATION
• Insulin: (Anabolic effect)– Targets osteoblasts directly.– Stimulates bone matrix formation and
mineralization.– Indirectly affects bone formation by a
stimulation of IGF-I produced in the liver.
REGULATION OF BONE FORMATION
• Growth Hormone: (Anabolic effect)– Required for attaining normal bone mass– Anabolic effect through IGF-I production.
REGULATION OF BONE FORMATION
• Glucocorticoids: (in vitro)– promotes differentiation of osteoblasts and
stimulate bone matrix formation.
REGULATION OF BONE FORMATION
• Glucocorticoids: (in vivo)
REGULATION OF BONE FORMATION
• Bone Morphogenetic Proteins:– Belong to TGF-β family.– Can induce chondrogenic and osteogenic
differentiation in undifferentiated mesenchymal cells.– Stimulating differentiation of more mature
osteoblasts.– Stimulate collagen production.– No marked effects on bone matrix formation.
REGULATION OF BONE FORMATION
• TGF-β:– Can act as a potent inhibitor of osteogenic
induction by BMP.– Strongly stimulates expression of matrix
proteins by osteoblastic cells.
REGULATION OF BONE FORMATION
• TGF-β:
REGULATION OF BONE FORMATION
• IGF-I and II: (Potent Anabolic Agents)– Similar effects like TGF-β on matrix proteins
and matrix metalloproteinases.– Also stimulates proliferation of Osteoblastic
cell precursors.
REGULATION OF BONE FORMATION
• Fibroblast growth factors : (Basic)– Increased proliferation of osteoprogenitors.– Promote osteogenic differentiation.
• PDGF:– Promotes osteogenesis as Fibroblast growth
Factors.– Also influences the expression of other
cytokines.
31
REGULATION OF BONE FORMATION
BONE RESORPTION
• Specialized cell : Osteoclast• Produced by the monocyte/macrophage
lineage of hematopoietic cells.
BONE RESORPTION
Receptor Activator of Nuclear Factor κB / Ligand
Osteoprotegerin Ligand
Hyaluronan
receptor
CD44
Fusion of monocytic precursors occurs at the site of bone resorption to form osteoclasts.
Fusion of monocytic precursors occurs at the site of bone resorption to form osteoclasts.
αvß 3 integrin with CD44
Highly expressed in
osteoclasts and osteoclasts precursors
Signaling cell attachment and also possibly for
osteoclast chemotaxis
(haptotaxis) & migration
BONE RESORPTION
1. Demineralization Phase
2. Degradation of matrix
BONE RESORPTION
1. Demineralization Phase
BONE RESORPTION
2. Degradation of matrix
1. Demineralization Phase
Lysosomal enzymesLysosomal enzymesMatrix metalloproteinases
activated under acidic conditions observed in
resorption lacunae
Matrix metalloproteinases activated under acidic conditions observed in
resorption lacunae
Can degrade matrix macromolecules, including collagen
BONE RESORPTION
Mechanism for limiting
resorptive activity.
Mechanism for limiting
resorptive activity.
BONE RESORPTION
REGULATION OF BONE RESORPTION
Calcitonin: Causes cytoplasmic contraction of the cell membrane in mature osteoclasts and their dissociation into monocytic cells
Regulate Osteoclast development through the OPG/OPGL/RANK pathway
REGULATION OF BONE RESORPTION
Stimulates proliferation of precursor cells.Indirectly via PGE2
BONE MODELING
VsBONE
REMODELING
• Modeling is the process used by bone to shape itself, rating an organ with maximal compressive strength, which is associated with the formation and growth of bones in childhood and adolescence.
BONE MODELING
Periodontology 2000, Vol. 14, 1997
BONE REMODELING
• Remodeling represents a change that occurs within the mineralized bone without a concomitant alteration of the architecture of the tissue.
Why Remodel Bone ???• Allows bone to respond to loads (stresses)• Allows repair of microdamage• Participates in serum Ca2+ regulation• Replacement of old bone with new bone
BONE REMODELING
– Forst HM-1964
IN NORMAL ADULTS
COUPLING
OsteoblastsOsteoblasts OsteoclastsOsteoclasts
BONE REMODELING HYPOTHESIS
• The number of sites entering the bone formation phase, called the activation frequency, together with the individual rates of the two processes, determines the rate of tissue turnover.
• Significance:– Resorption depth and mean wall thickness may vary by on 10-20%
of normal in different diseases– Activation frequency may vary by upto 50-100%.
• Thus, in most diseases, the activation frequency is the most important regulator of bone turnover and changes in the bone mass.
- Ericksen Ef, 1986
ACTIVATION FREQUENCY
BONE MULTICELLULAR UNITS (BMUs)A BMU is comprised of
(1) a front osteoclast residing on a surface of newly resorbed bone (the resorption front), (2) a compartment containing vessels and pericytes, and (3) a layer of osteoblasts present on a newly formed organic matrix (the deposition front).
Osteoclast (OC)Osteoblasts (OB) Osteoid (OS)Vascular structures (V)RL = reversal lineLB = lamellar bone
•Becomes “machinery” that remodels bone.•Forms in response to molecular signaling.•Functions over a period of weeks to months (10 m/day).
AGING & BONE
•Starts at the age of approximately 25-30 years, when maximal bone formation is achieve.
•From that age, a steady decline in bone mass begins for both men and women. (more severe in females)
•The decrease in bone mass leads to:•Thinning of cortical bone due to tunneling or trabeculation of the endosteal cortical envelope, with expansion of the marrow cavity accompanied by some gain in diameter.
Bone’s Role in Calcium Homeostasis
Bone’s Role in Calcium Homeostasis
Bone’s Role in Calcium HomeostasisSome
stimulus causes blood calcium level to decrease
Some stimulus
causes blood calcium level to decrease
Increase production of cAMP in
Parathyroid Gland
Increase production of cAMP in
Parathyroid GlandMore PTH
is secreted
More PTH is
secreted
Stimulates osteoblast to release IL-1 & IL-6
Stimulates osteoblast to release IL-1 & IL-6
Migration of monocyte to bone areas
Migration of monocyte to bone areas
LIF secreted by osteoblast
coalesces monocytes to
form osteoclast
LIF secreted by osteoblast
coalesces monocytes to
form osteoclast
Causes bone resorption &
release of calcium in
blood.
Negative fe
edback
Negative fe
edback
Turns Off
Turns Off
Alveolar Bone in Disease
Alveolar Bone in Disease
Clinical Implications
• Alveolar bone is dependent upon the presence of teeth for its preservation.
• Maintenance is also compromised by trauma and inflammatory episodes associated with periodontal disease.
• Rapid remodeling – important for movement of teeth in response to occlusive and orthodontic forces.
Clinical Implications
Site specific remodeling in the absence of inflammation.
Clinical Implications
Potential Therapeutic Strategies To Treat Bone Resorption
Potential Therapeutic Strategies To Treat Bone Resorption
Increases apoptosis of osteoclasts thus
reducing life spanFlurbiprofen & Ibuprofen Promotes apoptosisCurrent therapeutic agents
for osteoporosis.Also is used for coating
implant surface.
Block the initial osteoclast adhesion to
the matrix.
Reduce the protease degradation of the
organic matrix.
Conclusion
Conclusion
•Alveolar bone has interdependence with dentition.
•Constant state of Flux.
•Rate of remodeling is unique to alveolar bone and is important for its adaptability.
•Many of the factors that regulate bone remodeling like, Cbfa1 & Osteoprotegrin, appear to exert their effects either directly or indirectly through these genes, which have become important targets for developing pharmacological and clinical strategies to regulate the rate of bone formation and resorption that will be important for maintenance of a healthy periodontium.
• Carranza’s Clinical Periodontology, 10th edition.• Periodontology 2000 Vol. 3, 1993• Periodontology 2000 Vol. 13, 1997• Periodontology 2000 Vol. 14, 1997• Periodontology 2000 Vol. 24, 2000• Periodontology 2000 Vol. 41, 2006• Principles of Anatomy & Physiology, 11th edition, by
Tortora & Derrickson.• Clinical Periodontology & Implant Dentistry, 5th edition,
Jan Lindhe
References
Thank You
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