RANKL-RANK/OPG MOLECULAR COMPLEX
RANKL-RANK/OPG MOLECULAR COMPLEX
A remodelação óssea é um processo fisiológico cíclico e contínuo , o que garante a conservação e a renovação da matriz óssea. Osteossíntese da matriz óssea é atingido pelos osteoblastos e coordenadas dentro desta máquina complexa de remodelação óssea com reabsorção da matriz óssea extracelular realizada por osteoclastos. O fenótipo, função e ontogênese dos osteoblastos e osteoclastos são essencialmente diferentes. Osteoblastos surgem de células da medula óssea estroma, e dos osteoclastos surgem células progenitoras hematopoéticas mielóides/ monócitos / macrófagos. Ambos os tipos de células têm um objectivo comum - a estrutura óssea. O desequilíbrio entre as atividades efetoras de osteoblastos e osteoclastos tem implicações clínicas associadas com a diminuição ou aumento da densidade mineral óssea em massa, osteoporose ou osteopenia respectivamente. Relatórios de 1977-1988 ofereceu novas explicações que mudaram a percepção sobre o metabolismo ósseo e abriu novas interpretações immunoclinical com perspectivas terapêuticas. O equilíbrio do complexo trimolecular composto de Osteoprotegerin (OPG), RANKL (osteoprotegerina-ligante) e RANK, que são fatores de controle através da modulação osteoclastogênese, regula a homeostase da remodelação óssea. Estas moléculas, OPG, RANK e RANKL, funcionam como receptores e ligantes e pertencem à superfamília do fator de necrose tumoral (TNF). Palavras-chave: remodelação óssea, metabolismo ósseo, complexo trimolecular - OPG / RANKL-RANK.
REFERÊNCIA:
1. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation
factor is a ligand for osteoprotegrin/osteoclastogenesis
inhibitory factor and is identical to TRANCE/RANKL. Proc
Natl Acad Sci USA 1998;95:3557-60.
2. Lacey DL, Timms E, Tan HL, et al. Osteoprotegrin ligand is a
cytokine that regulates osteoclast differentiation and activation.
Cell 1998;93:165-76.
3. Anderson DM, Maraskovsky E, Bilingsley WI, et al. A homologue
of the TNF receptor and its ligand enhance T-cell growth and
dendritic cell function. Nature 1997;390:175-9.
4. Wong BR, Rho J, Arron J, et al. TRANCE is a novel ligand of the
tumor necrosis factor receptor family that activates C-Jan Nterminal
kinase in T cells. J Biol Chem 1997;2372:21590-4.
5. Kong Y, Yoshida H, Sarasi I, et al. OPGL is a key regulation of
osteoclastogenesis, lymphocyte development and lymph-node
organogenesis. Nature 1999;397:315-23.
6. Burgess TL, Qian Y, Kaufman S, et al. The ligand for osteoprotegrin
(OPGL) directly activates mature osteoclasts. J Cell Biol
1999;145:527-38.
7. Lum L, Wong BR, Jasien R, et al. Evidence for a role of a tumor
necrosos factor-alpha (TNF-alpha) converting enzyme-like
protease in shedding of TRANCE, a TNF family member involved
in osteoclastogenesis and dendritic cell survival. J Biol Chem
1999;274:13613-18.
8. Zhang Y, Heulsmann A, Tandravi M. TNF-alpha stimulator RANKLinducer
osteoclastogenesis via conpling of TNF type 1 receptor
and RANK signaling Pathway. J Biol Chem 2001;276:563-8.
9. Aubin JE, Bonnelye E. Osteoprotegrin and its ligand: a new paradigm
for regulation of osteoclastogenesis and bone resorbsion.
Osteoporos Int 11: 905-13.
10. Kong YY, Boyle WJ, Penninger JM. Osteoprotegrin ligand a
regulator of immune responses and bone physiology. Im Today
2000;21(10):495-502.
11. Roodman GD. Cell biology of the osteoclast. Exp Hematol
1999;27:1229-41.
12. Hhsu H, Lacey DL, et al. Tumor necrosis factor receptor family
member RANK mediates osteoclast differentiation and activation
induced by osteoprotegrin ligand. Proc Natl. Acad Sci USA
1999;96:3540-45.
13. Nakagawa N, Kinosaki M, Yamaguchi K, et al. RANK is the esential
signaling receptor for osteoclast differentiation factor in osteoclastogenesis.
Biochem Biophys Res Commun 1998;253:395-400.
14. Li J, Sarosi I, Yan XQ, et al. RANK is the intrinsec hematopoetic
cell surface receptor that controls osteoclastogenesis and
regulation of bone mass and calcium metabolism. Proc Natl Acad
Sci USA 2000;97:1566-71.
15. Darnay BG, Haridas V, Ni J. Characterization of the intracellular
domain of receptor activator of NF-kappaB (RANK). Interaction
with tumor necrosis factor receptor associated factors and
activation of NF-kappaB and c-Jun N-terminal kinase. J Biol
Chem 1998;273:20551-5.
16. Kabayashi N, Kadano Y, Naito A, et al. Segregation of TRAF-6-
mediated signaling pathways clarilies its role in osteoclastogenesis.
EMBO J. 2001;20:1271-80.
17. Pettit AR, Ji H, von Stechow D, et al. TRANCE/RANKLknokout
mice are protected from bone erosion in the K/BxN serum
transfer model of arthritis. Am J Pathol 2001;159:1689-99.
18. Abu-Amer Y. IL-4 abrogates osteoclastogenesis throught STAT5-
dependent inhibition of NF-kappaB. J Clin Invest 2001;107:1375-
85.
19. Simonet WS, Lucey DL, Dunstan CR, et al. Osteoprotegrin: a novel
secreted protein involved in the regulation of bone density.
Cell 1997;89:909-19.
20. Suda T, Nakamusa I, et al. Regulation of osteoclast function. J Bone
Min Res 1997;12:869-79.
21. Yasuda H, Shima N, et al. Identity of osteoclastogenesis inhibitory
factor (OCIF) and osteoprotegrin (OPG): a mechanism by which
OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology
1998;139:1329-37.
22. Bucay N, Sarosi I, Dunstar CR, et al. Osteoprotegrin - deficent
302 TMJ 2003, Vol. 53, No. 3-4
mice develop early onset osteoporozis and arterial calcification.
Genes Rev 1998;12:1260-8.
A remodelação óssea é um processo fisiológico cíclico e contínuo , o que garante a conservação e a renovação da matriz óssea. Osteossíntese da matriz óssea é atingido pelos osteoblastos e coordenadas dentro desta máquina complexa de remodelação óssea com reabsorção da matriz óssea extracelular realizada por osteoclastos. O fenótipo, função e ontogênese dos osteoblastos e osteoclastos são essencialmente diferentes. Osteoblastos surgem de células da medula óssea estroma, e dos osteoclastos surgem células progenitoras hematopoéticas mielóides/ monócitos / macrófagos. Ambos os tipos de células têm um objectivo comum - a estrutura óssea. O desequilíbrio entre as atividades efetoras de osteoblastos e osteoclastos tem implicações clínicas associadas com a diminuição ou aumento da densidade mineral óssea em massa, osteoporose ou osteopenia respectivamente. Relatórios de 1977-1988 ofereceu novas explicações que mudaram a percepção sobre o metabolismo ósseo e abriu novas interpretações immunoclinical com perspectivas terapêuticas. O equilíbrio do complexo trimolecular composto de Osteoprotegerin (OPG), RANKL (osteoprotegerina-ligante) e RANK, que são fatores de controle através da modulação osteoclastogênese, regula a homeostase da remodelação óssea. Estas moléculas, OPG, RANK e RANKL, funcionam como receptores e ligantes e pertencem à superfamília do fator de necrose tumoral (TNF). Palavras-chave: remodelação óssea, metabolismo ósseo, complexo trimolecular - OPG / RANKL-RANK.
REFERÊNCIA:
1. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation
factor is a ligand for osteoprotegrin/osteoclastogenesis
inhibitory factor and is identical to TRANCE/RANKL. Proc
Natl Acad Sci USA 1998;95:3557-60.
2. Lacey DL, Timms E, Tan HL, et al. Osteoprotegrin ligand is a
cytokine that regulates osteoclast differentiation and activation.
Cell 1998;93:165-76.
3. Anderson DM, Maraskovsky E, Bilingsley WI, et al. A homologue
of the TNF receptor and its ligand enhance T-cell growth and
dendritic cell function. Nature 1997;390:175-9.
4. Wong BR, Rho J, Arron J, et al. TRANCE is a novel ligand of the
tumor necrosis factor receptor family that activates C-Jan Nterminal
kinase in T cells. J Biol Chem 1997;2372:21590-4.
5. Kong Y, Yoshida H, Sarasi I, et al. OPGL is a key regulation of
osteoclastogenesis, lymphocyte development and lymph-node
organogenesis. Nature 1999;397:315-23.
6. Burgess TL, Qian Y, Kaufman S, et al. The ligand for osteoprotegrin
(OPGL) directly activates mature osteoclasts. J Cell Biol
1999;145:527-38.
7. Lum L, Wong BR, Jasien R, et al. Evidence for a role of a tumor
necrosos factor-alpha (TNF-alpha) converting enzyme-like
protease in shedding of TRANCE, a TNF family member involved
in osteoclastogenesis and dendritic cell survival. J Biol Chem
1999;274:13613-18.
8. Zhang Y, Heulsmann A, Tandravi M. TNF-alpha stimulator RANKLinducer
osteoclastogenesis via conpling of TNF type 1 receptor
and RANK signaling Pathway. J Biol Chem 2001;276:563-8.
9. Aubin JE, Bonnelye E. Osteoprotegrin and its ligand: a new paradigm
for regulation of osteoclastogenesis and bone resorbsion.
Osteoporos Int 11: 905-13.
10. Kong YY, Boyle WJ, Penninger JM. Osteoprotegrin ligand a
regulator of immune responses and bone physiology. Im Today
2000;21(10):495-502.
11. Roodman GD. Cell biology of the osteoclast. Exp Hematol
1999;27:1229-41.
12. Hhsu H, Lacey DL, et al. Tumor necrosis factor receptor family
member RANK mediates osteoclast differentiation and activation
induced by osteoprotegrin ligand. Proc Natl. Acad Sci USA
1999;96:3540-45.
13. Nakagawa N, Kinosaki M, Yamaguchi K, et al. RANK is the esential
signaling receptor for osteoclast differentiation factor in osteoclastogenesis.
Biochem Biophys Res Commun 1998;253:395-400.
14. Li J, Sarosi I, Yan XQ, et al. RANK is the intrinsec hematopoetic
cell surface receptor that controls osteoclastogenesis and
regulation of bone mass and calcium metabolism. Proc Natl Acad
Sci USA 2000;97:1566-71.
15. Darnay BG, Haridas V, Ni J. Characterization of the intracellular
domain of receptor activator of NF-kappaB (RANK). Interaction
with tumor necrosis factor receptor associated factors and
activation of NF-kappaB and c-Jun N-terminal kinase. J Biol
Chem 1998;273:20551-5.
16. Kabayashi N, Kadano Y, Naito A, et al. Segregation of TRAF-6-
mediated signaling pathways clarilies its role in osteoclastogenesis.
EMBO J. 2001;20:1271-80.
17. Pettit AR, Ji H, von Stechow D, et al. TRANCE/RANKLknokout
mice are protected from bone erosion in the K/BxN serum
transfer model of arthritis. Am J Pathol 2001;159:1689-99.
18. Abu-Amer Y. IL-4 abrogates osteoclastogenesis throught STAT5-
dependent inhibition of NF-kappaB. J Clin Invest 2001;107:1375-
85.
19. Simonet WS, Lucey DL, Dunstan CR, et al. Osteoprotegrin: a novel
secreted protein involved in the regulation of bone density.
Cell 1997;89:909-19.
20. Suda T, Nakamusa I, et al. Regulation of osteoclast function. J Bone
Min Res 1997;12:869-79.
21. Yasuda H, Shima N, et al. Identity of osteoclastogenesis inhibitory
factor (OCIF) and osteoprotegrin (OPG): a mechanism by which
OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology
1998;139:1329-37.
22. Bucay N, Sarosi I, Dunstar CR, et al. Osteoprotegrin - deficent
302 TMJ 2003, Vol. 53, No. 3-4
mice develop early onset osteoporozis and arterial calcification.
Genes Rev 1998;12:1260-8.
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