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Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions.
J Bone Miner Res. 2001 Oct; 16(10):1787-94.JB

Abstract

Transforming growth factor beta (TGF-beta) is abundant in bone and has complex effects on osteolysis, with both positive and negative effects on osteoclast differentiation, suggesting that it acts via more than one mechanism. Osteoclastogenesis is determined primarily by osteoblast (OB) expression of the tumor necrosis factor (TNF)-related molecule receptor activator of NF-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), which are increased and decreased, respectively, by osteolytic factors. A RANKL-independent osteoclastogenic mechanism mediated by TNF-alpha has also been shown. Therefore, we investigated TGF-beta effects on osteoclast formation in culture systems in which osteoclastogenic stimulus is dependent on OBs and culture systems where it was provided by exogenously added RANKL or TNF-alpha. Both OPG and TGF-beta inhibited osteoclast formation in hemopoietic cell/OB cocultures, but the kinetics of their action differed. TGF-beta also inhibited osteoclastogenesis in cocultures of cells derived from OPG null (opg-/-) mice. TGF-beta strongly decreased RANKL messenger RNA (mRNA) expression in cultured osteoblasts, and addition of exogenous RANKL to TGFbeta-inhibited cocultures of opg-/- cells partially restored osteoclastogenesis. Combined, these data indicate that the inhibitory actions of TGF-beta were mediated mainly by decreased OB production of RANKL. In contrast, in the absence of OBs, TGF-beta greatly increased osteoclast formation in recombinant RANKL- or TNF-alpha-stimulated cultures of hemopoietic cells or RAW 264.7 macrophage-like cells to levels several-fold greater than attainable by maximal stimulation by RANKL or TNF-alpha. These data suggest that TGF-beta may increase osteoclast formation via action on osteoclast precursors. Therefore, although RANKL (or TNF-alpha) is essential for osteoclast formation, factors such as TGF-beta may powerfully modify these osteoclastogenic stimuli. Such actions may be critical to the control of physiological and pathophysiological osteolysis.

Authors+Show Affiliations

Department of Medicine, St. Vincent's Institute of Medical Research and The University of Melbourne, Fitzroy, Victoria, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11585342

Citation

Quinn, J M., et al. "Transforming Growth Factor Beta Affects Osteoclast Differentiation Via Direct and Indirect Actions." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 16, no. 10, 2001, pp. 1787-94.
Quinn JM, Itoh K, Udagawa N, et al. Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. J Bone Miner Res. 2001;16(10):1787-94.
Quinn, J. M., Itoh, K., Udagawa, N., Hausler, K., Yasuda, H., Shima, N., Mizuno, A., Higashio, K., Takahashi, N., Suda, T., Martin, T. J., & Gillespie, M. T. (2001). Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 16(10), 1787-94.
Quinn JM, et al. Transforming Growth Factor Beta Affects Osteoclast Differentiation Via Direct and Indirect Actions. J Bone Miner Res. 2001;16(10):1787-94. PubMed PMID: 11585342.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. AU - Quinn,J M, AU - Itoh,K, AU - Udagawa,N, AU - Hausler,K, AU - Yasuda,H, AU - Shima,N, AU - Mizuno,A, AU - Higashio,K, AU - Takahashi,N, AU - Suda,T, AU - Martin,T J, AU - Gillespie,M T, PY - 2001/10/5/pubmed PY - 2002/2/28/medline PY - 2001/10/5/entrez SP - 1787 EP - 94 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 16 IS - 10 N2 - Transforming growth factor beta (TGF-beta) is abundant in bone and has complex effects on osteolysis, with both positive and negative effects on osteoclast differentiation, suggesting that it acts via more than one mechanism. Osteoclastogenesis is determined primarily by osteoblast (OB) expression of the tumor necrosis factor (TNF)-related molecule receptor activator of NF-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), which are increased and decreased, respectively, by osteolytic factors. A RANKL-independent osteoclastogenic mechanism mediated by TNF-alpha has also been shown. Therefore, we investigated TGF-beta effects on osteoclast formation in culture systems in which osteoclastogenic stimulus is dependent on OBs and culture systems where it was provided by exogenously added RANKL or TNF-alpha. Both OPG and TGF-beta inhibited osteoclast formation in hemopoietic cell/OB cocultures, but the kinetics of their action differed. TGF-beta also inhibited osteoclastogenesis in cocultures of cells derived from OPG null (opg-/-) mice. TGF-beta strongly decreased RANKL messenger RNA (mRNA) expression in cultured osteoblasts, and addition of exogenous RANKL to TGFbeta-inhibited cocultures of opg-/- cells partially restored osteoclastogenesis. Combined, these data indicate that the inhibitory actions of TGF-beta were mediated mainly by decreased OB production of RANKL. In contrast, in the absence of OBs, TGF-beta greatly increased osteoclast formation in recombinant RANKL- or TNF-alpha-stimulated cultures of hemopoietic cells or RAW 264.7 macrophage-like cells to levels several-fold greater than attainable by maximal stimulation by RANKL or TNF-alpha. These data suggest that TGF-beta may increase osteoclast formation via action on osteoclast precursors. Therefore, although RANKL (or TNF-alpha) is essential for osteoclast formation, factors such as TGF-beta may powerfully modify these osteoclastogenic stimuli. Such actions may be critical to the control of physiological and pathophysiological osteolysis. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/11585342/Transforming_growth_factor_beta_affects_osteoclast_differentiation_via_direct_and_indirect_actions_ L2 - https://doi.org/10.1359/jbmr.2001.16.10.1787 DB - PRIME DP - Unbound Medicine ER -