The document discusses the alveolar bone, which forms, supports, and protects the teeth. It has three parts: the alveolar bone proper, compact bone, and cancellous bone. Its functions include supporting teeth, attaching muscles, housing bone marrow, and storing ions. The alveolar bone is made up of water, organic components like collagen and cells, and inorganic hydroxyapatite crystals and ions. Osteoblasts form bone by synthesizing an uncalcified bone matrix and depositing hydroxyapatite crystals, while osteoclasts resorb bone by secreting acids and enzymes to dissolve the mineral and collagen phases.

1. Dr Gauri Kapila
MDS Student
Department of Periodontology and Oral
Implantology

3.  Portion of maxilla and mandible that forms, supports
& protects the teeth
 Parts – alveolar bone proper, compact bone,
cancellous bone
FUNCTIONS
 Support to teeth
 Attachment to muscles
 Framework for bone marrow
 Reservoir of ions

4. Water (15%)
Organic component (25%)
-Collagen І (90%)
-Proteins (osteocalcin, osteonectin, osteopontin, proteoglycans)
-Cells (osteoprogenitor cells, osteoblasts, osteoclasts, osteocytes, bone
lining cells)
Inorganic component (60%)
-Hydroxyapatite
- Ions

5. • Synthesis of uncalcified matrix or
osteoid
• Deposition of hydroxyapatite
crystals
Bone formation
OSTEOBLASTS
• Secretion of acid for dissolution
of mineral phase
• Secretion of Cathepsin B & L for
removal of collagenous matrix
Bone
resorption
OSTEOCLASTS
BONE TURNOVER

6.  Osteo-progenitor cells
 Osteoblasts
 Osteoclasts
 Osteocytes
 Bone lining cells

7. Development of
bones
Replacement of
primary dentition
with secondary
Osseointegration
of implants
Physiological
drift of the teeth
Response to
occlusal &
orthodontic
forces

8. • Osteoblasts
• Cytokines
• RANKL
• M-CSF
• Osteoclast differentiation
Kobayashi and Udagawa
2007
• Stimulated osteoblasts >
Procollagenase
• Removal of collagenous
part of bone
• Osteoclasts > resorption of
mineralized part of bone
INTERRELATIONSHIP

10. Systemic
hormones
-Parathyroid hormone
-Vitamin D3
-Calcitonin
Local produced
factors
-PGE2
-Leukotrines
-Cytokines : IL2 IL3 & IL6
-Growth factors : TNFα
TNFβ TGFβ PDGF

11. Multipotent stromal stem cells
Plating and attachment
Express Col І, II, III and alkaline phosphatase & osteopontin
Increased synthesis of ColІ and alkaline phosphatase
Diminishing of Col II & Col III synthesis
Formation of collagen substratum

12. Declining of bone osteopontin
Pre-osteoblast > osteoblast through interaction with α2β1 receptor
Condensation of mesenchymal cells
Emergence of osteoblasts
Expression of bone sialoprotein
Initiation of mineralization

13. Increased osteocalcin synthesis
Osteoblasts > osteocytes and bone lining cells
Xiao G, Wang D, Benson MD, Karsenty G, Franceschi RT
Role of the alpha2-integrin in osteoblast-specific gene expression
and activation of the Osf2 transcription factor. J
Biol Chem 1998: 273: 32988–32994

15. Homeobox
genes
hoxa2, hoxa13,
hoxd13, dlx5,
msx1, msx2
Regulatory
genes
Runx2
Cbfa1- Master
gene for
osteogenic
differentiation
Transcription
factors
•Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997).
Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation.
Cell 1997: 89: 747–754
•Rodan GA, Harada S. The missing bone. Cell 1997: 89:
677–680.

16.  Why runx2/cbfa1 is considered to be the master gene for
osteogenic differentiation?
 Functional role in the differentiation of all mineralizing
tissue cells
 Deletion of cbfa1 results in absence of ossified tissues
 Heterozygous mutations of gene causes cleidocranial
dysplasia in humans
•Jiang H, Sodek J, Karsenty G, Thomas H, Ranly D, Chen J. Expression of
core binding factor Osf2/Cbfa-1 and bone sialoprotein in tooth
development. Mech Dev 1999: 81:169–173.

17.  Studies in vitro have shown bone morphogenetic
protein-2 treatment of the myogenic cell line
C2C12 transiently upregulates cbfa1 and Msx-2
 While TGF-β can also increase cbfa1 and
suppresses myogenic differentiation in these cells,
osteogenic differentiation does not occur,
indicating that other factors induced by BMP’s are
necessary for complete expression of the
osteoblastic phenotype
Lee M-H, Javed A, Kim H-J, Shin H-I et al. Transient upregulation of
CBFA1 in response to bone morphogenetic protein-2 and transforming
growth factor b1 in C2C12 myogenic cells coincides with suppression
of the myogenic phenotype but is not sufficient for osteoblastic
differentiation. J Cell Biochem 1999: 73:114–125.

18.  A potential factor homeobox-containing gene
dlx5 regulates
osteoblast differentiation which is induced by BMP-4
 Treatment of undifferentiated cells with BMP-7/OP-1, signal
through Smad 5, has also identified BMP/OP-1 responsive
gene and a transcription factor, AJ-18 as immediate targets of
BMP-7, in osteogenic systems
Tamaki K, Souchelnytskyi S, Itoh S, Nakao A et al. Intracellular signaling
of osteogenic protein-1 through Smad5 activation. J Cell Physiol
1998: 177: 355–363.

19.  Recent studies indicate that the transcriptional activities of
Smads and core binding factor a1 may be linked by the
formation of regulatory complexes which may include other
transcription factors.
Hanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, Guo
WH, Imamura T et al. Interaction and function cooperation of
PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin
germline Ca promoter. Biol Chem 1999: 274: 31577–31582.

20. REGULATION OF BONE FORMATION
Calcium
metabolism
hormones
CALCITONIN
PARATHYROID
HORMONE
VITAMIN-D
TGF-β
Insulin like
growth factor
Glucocorticoids
Thyroid
hormones
FGF
PDGF
Bone
morphogenetic
proteins
Estrogen

21. Production of osteoblastic cells
Activity of osteoblastic cells
Bone resorption, directly or indirectly

22. PARATHYROID HORMONE
Anabolic effect
Stimulates bone
formation through
TGF-β & insulin like
growth factor
Catabolic effect
Stimulates bone
resorption indirectly
(coupling)
Increased serum Ca
Canalis E, Hock JM, Raisz LG. Parathyroid hormone: Anabolic and
catabolis effects on bone and interactions with growth factors. In:
Bilezikian JP, Marcus R, Levine MA, ed.
The parathyroids. New York: Raven Press, 1994: 65–82.

23. VITAMIN D3
Anabolic effect
Primary function in Ca
absorption from
intestine
Stimulates synthesis of
osteocalcin &
osteopontin
Catabolic effect
Stimulates bone
resorption
Suppresses collagen
production
DeLuca HF. Vitamin D revisited. Clin Endocrinol Metab 1980: 9: 1–26.

24. GLUCOCORTICOIDS
Anabolic
effect
Promotes
differentiation of
osteoblastic cells
Stimulates bone
matrix formation
Catabolic
effect
Prolonged t/t with GC
causes bone loss due
to inc PTH in
response to
inhibitory effect on
Ca absorption

25. TGF-β
Anabolic effect
Induces osteogenic
differentiation of
mesenchymal cells
Decrease in matrix
degradative activity
through inhibtion of
MMP’s
Catabolic effect
Inhibits osteogenic
induction by BMP’s
Reddi AH. BMPs: actions in flesh and bone. Nat Med 1997:
3: 837–839.

26. INSULIN
Anabolic effect
Directly targets osteoblasts
Stimulates bone matrix formation and
mineralization
Stimulates insulin like GF produced in liver

27. THYROID HORMONE
Anabolic effect
Affects endochondral bone formation by its
action on cartilage formation

28. BONE MORPHOGENETIC PROTEINS
Anabolic effect
Most profound effect on bone formation

29. INSULIN LIKE GROWTH FACTOR
Anabolic effect
Stimulates proliferation of osteoblast
precursors
Inhibits MMP’s
Hock JM, Centrella M, Canalis E. Insulin-like growth factor I (IGF-I) has
independent effects on bone matrix formation and cell replication.
Endocrinology 1988: 122:254–260.

30. PDGF AND FGF
Anabolic effect
Increases proliferation of osteoprogenitor cells
Promote osteogenic differentiation
Influence expression of other cytokines
Help in wound and fracture healing
Hock JM, Canalis E. Platelet-derived growth factor enhances
bone cell replication but not differentiated function
of osteoblasts. Endocrinology 1994: 134: 1423–1428.

31.  Requires recruitment of a specialized cell, produced
by the monocyte/macrophage lineage of
hematopoietic cells derived from bone marrow
 develop from a pluripotential mononuclear
precursor CFU-GM which is stimulated to proliferate
and differentiate
under the influence of M-CSF

32. STAGES IN THE LIFE CYCLE OF AN OSTEOCLAST

35.  Recent molecular studies have identified transcription
factors, such as c-Fos and PU.1, that are required for
osteoclast differentiation
 Studies stating that if there is impaired production of
colony-stimulating factor-1 (CSF-1), osteoclasts fail to form
leading to osteopetrosis
 Studies showing osteopetrotic phenotype resulting from
ablation of c-Fos gene, revealing the importance of these
genes in the early development of osteoclasts
Studies on transcription factors required for osteoclast
differentiation
Boyce BF, Hughes DE, Wright KR, Xing L, Dai A. Recent advances in
bone biology provide insight into the pathogenesis of bone diseases.
Lab Invest 1999: 79: 83–94

36.  The identification of a novel receptor, termed OPG has
recently uncovered a key regulatory mechanism in
osteoclast differentiation and activity
 OPGL-the putative osteoclast differentiation factor-
expressed on the surface of stromal/bone cells-causes
differentiation-through TNFR or ODAR or RANK
 Decoy receptor that binds ligand but is incapable of
signaling
 Ablation-osteoporosis
 Increased expression-osteopetrosis
Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS,
Osteoprotegerin: a novel secreted protein involved in the
regulation of bone density. Cell 1997: 89: 309–319.

37.  Osteocytic osteolysis
 Osteoclastic resorption

38.  Formation of osteoclasts involves fusion of
monocytic precursors which occurs at the site of
bone resorption
 CD44 (hyaluronan receptor), the aγb3 integrin is
highly expressed in osteoclasts; both receptors-
primary target for the bone matrix protein
osteopontin in signaling, cell attachment and
migration

39. PHASES OF RESORPTION
Ten cate’s description of sequence of events

40.  On the bone surface, osteoclasts attach & become
polarized, form a ruffled border beneath which bone
resorption takes place
 Acidic environment- adenosine triphosphatase,
pumps protons generated by carbonic anhydrase
activity
 Demineralization exposes organic matrix
DEMINERALISATION PHASE

41.  Lysosomal enzymes can degrade collagen matrix
macromolecules into its constituent amino acids- by
phagocytic degradation & release of enzymes- acid
phosphatase & cathepsin
 Matrix metalloproteinases-activated under the acidic
conditions-resorption lacunae & contribute to matrix
degradation
MATRIX DEGRADATION
Sodek J, Overall CM. Matrix metalloproteinases in periodontal tissue
remodelling. Matrix 1992: 1(suppl): 352–362.

42.  Sequestration of mineral ions & amino acids takes
place inside osteoclast
 Osteoclasts undergo apoptosis-mechanism for
limiting resorptive activity
APOPTOSIS OF OSTEOCLASTS

43. Stimulating factors
PTH
Vit-D3
IL-1
IL-6
TNF-α
Inhibiting factors
Calcitonin
TGF-β
Estrogen
Interferon-γ

44. Parathyroid
hormone
Affects indirectly by acting on
the receptors present on pre-
osteoblasts, osteoblasts & lining
cells
Vitamin D3
Mediated by bone matrix protein
osteopontin by its ligation to αγβ3
receptor in pre-osteoclasts & osteoclasts
modulating development of osteoclasts
through OPG/OPGL/RANK pathway
IL-1 & TNF-α
Pro inflammatory cytokine
that upregulates osteoclastic
activity
IL-6
Produced by osteoblasts in
response to PTH & VitD3
Related to estrogen deficiency
related bone resorption
Horwood NJ, Elliott J, Martin TJ, Gillespie MT. Osteotropic
agents regulate the expression of osteoclast differentiation
factor and osteoprotegerin in osteoblastic stromal
cells. Endocrinology 1998: 139: 4743–4746.

45. Calcitonin
Inhibits osteoclastic activity-causes
cytoplasmic contraction of cell
membrane resulting in dissociation
into monocytic cells
Estrogen
Suppresses production of bone
resorbing cytokines IL-1 and IL-6
Interferon γ & TNF-β
Downregulates the differentiation
of osteoclasts
Takahashi S, Goldring S, Katz M, Hilsenbeck S, Williams R, Roodman GD.
Down regulation of calcitonin during human osteoclast-like cell
differentiation. J Clin Invest1995: 95: 167–171.

46. Decrease in blood
Ca
Receptors on PT
glands release PTH
PTH stimulates
osteoblasts
Osteoblasts
release IL-1 & IL-6
Stimulates
monocytes to
migrate to bone
area
LIF coalsces
monocytes into
multinucleated
osteoclasts
Osteoclasts resorb
bone
Release of Ca ions
from
hydroxyapatite
into blood
Blood Ca is
normalised

47. Breakdown of collagen releases osteogenic
substrates
Stimulates differentiation of osteoblasts
Osteoblasts deposit bone

50. INHIBITION OF RANKL-RANK INTERACTION
 Development of OPG-fc fusion protein and Denosumab-
fully human monoclonal antibody with high affinity for
RANKL
 A peptide WP9QY shown to inhibit RANKL
INHIBITION OF SIGNALING MOLECULES IN OSTEOCLASTIC
PRECURSORS
 A peptide inhibitor of IkB kinase inhibiting nFkB activation
 Blocking of Ca signaling resulting in blocking of NFATc1
expression
 Diphenylhydantoin (phenytoin) & other Ca channel
blockers block NFATc1 expression
INHIBITION OF OSTEOCLASTIC FUNCTION
 Bisphosphonates cause apoptosis of osteoclasts (oral)
 Calcitonin & Cathepsin inhibitors

51. 1. Xiao G, Wang D, Benson MD, Karsenty G, Franceschi RT
Role of the alpha2-integrin in osteoblast-specific gene expression
and activation of the Osf2 transcription factor. J
Biol Chem 1998: 273: 32988–32994
2. Yoshida H, Hayashi S, Kunisada T, Ogawa M et al The murine
mutation osteopetrosis is in the coding region of the macrophage
colony stimulating factor gene. Nature 1990:345: 442–444
•3. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997).
Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation.
Cell 1997: 89: 747–754
•Rodan GA, Harada S. The missing bone. Cell 1997: 89:
677–680.
4. Jiang H, Sodek J, Karsenty G, Thomas H, Ranly D, Chen J. Expression
of core binding factor Osf2/Cbfa-1 and bone sialoprotein in tooth
development. Mech Dev 1999: 81:169–173
5. Komori T, Yagi H, Nomura S, Yamaguchi A et al. Targeted disruption
of Cbfa1 results in a complete lack of bone formation owing to
maturational arrest of osteoblasts. Cell 1997: 89: 755–764.

52. 6. Mundlos S, Otto F, Munlos C, Mulliken JB et al. Mutations
involving the transcription factor CBFA1 cause cleidocranial
dysplasia. Cell 1997: 89: 773–779
7. Lee M-H, Javed A, Kim H-J, Shin H-I et al. Transient upregulation of
CBFA1 in response to bone morphogenetic protein-2 and transforming
growth factor b1 in C2C12 myogenic cells coincides with suppression
of the myogenic phenotype but is not sufficient for osteoblastic
differentiation. J Cell Biochem 1999: 73:114–125.
8. Miller SC, Jee WSS. The bone lining cell: a distinct phenotype?
Calcified Tissue Int 1987: 41: 1–5.
9. Takeda K, Ichijo H, Fujii M, Mochida Y et al. Identification of a novel
bone morphogenetic protein-responsive gene that may and a novel
zinc finger transcription factor: AJ-18(110), as immediate targets of
bone morphogenetic protein function as a noncoding RNA. J Biol Chem
1998 273:17079–85
10. Canalis E, Hock JM, Raisz LG. Parathyroid hormone: Anabolic and
catabolis effects on bone and interactions with growth factors. In:
Bilezikian JP, Marcus R, Levine MA, ed.
The parathyroids. New York: Raven Press, 1994: 65–82.

53. 11. DeLuca HF. Vitamin D revisited. Clin Endocrinol Metab 1980: 9: 1–
26.
12. Reddi AH. BMPs: actions in flesh and bone. Nat Med 1997:
3: 837–839
13. Hock JM, Centrella M, Canalis E. Insulin-like growth factor I (IGF-I)
has independent effects on bone matrix formation and cell
replication. Endocrinology 1988: 122:254–260.
14. Hock JM, Canalis E. Platelet-derived growth factor enhances
bone cell replication but not differentiated function
of osteoblasts. Endocrinology 1994: 134: 1423–1428.
15. Hock JM, Canalis E. Platelet-derived growth factor enhances
bone cell replication but not differentiated function
of osteoblasts. Endocrinology 1994: 134: 1423–1428.
16. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS,
Osteoprotegerin: a novel secreted protein involved in the
regulation of bone density. Cell 1997: 89: 309–319.
17. Sodek J, Overall CM. Matrix metalloproteinases in periodontal
tissue remodelling. Matrix 1992: 1(suppl): 352–362.

54. 18. Horwood NJ, Elliott J, Martin TJ, Gillespie MT. Osteotropic
agents regulate the expression of osteoclast differentiation
factor and osteoprotegerin in osteoblastic stromal
cells. Endocrinology 1998: 139: 4743–4746.
19. Takahashi S, Goldring S, Katz M, Hilsenbeck S, Williams R,
Roodman GD. Down regulation of calcitonin during human
osteoclast-like cell differentiation. J Clin Invest1995: 95: 167–171.

55.  Clinical Periodontology by Michael G. Newman, DDS,
Henry Takei, DDS, MS, Perry R. Klokkevold, DDS, MS and
Fermin A. Carranza 11th edition
 Periodontics by Barry M. Elly and Julius David Manson
 Periodontology 2000 Vol. 24,2000, 99-126
Molecular and Cellular biology of alveolar bone
 Periodontology 2000, Vol. 54, 2010, 235–246 Osteoclastic
bone resorption induced by innate responses

56. THANK YOU