Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions
| Autor: | Julian M.W. Quinn, Thomas J. Martin, K. Itoh, Kanji Higashio, Matthew T. Gillespie, K D Hausler, Atsuko Mizuno, Tatsuo Suda, H. Yasuda, Nobuyuki Udagawa, N. Takahashi, N. Shima |
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| Rok vydání: | 2001 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Endocrinology Diabetes and Metabolism Cellular differentiation Osteoclasts Receptors Cytoplasmic and Nuclear Receptors Tumor Necrosis Factor Mice Osteoprotegerin Osteoclast Transforming Growth Factor beta Internal medicine medicine Animals Orthopedics and Sports Medicine Cells Cultured Glycoproteins Mice Knockout Membrane Glycoproteins biology Receptor Activator of Nuclear Factor-kappa B Tumor Necrosis Factor-alpha RANK Ligand Osteoblast Cell Differentiation Transforming growth factor beta Coculture Techniques Cell biology Mice Inbred C57BL medicine.anatomical_structure Endocrinology RANKL biology.protein Carrier Proteins Spleen Transforming growth factor |
| Zdroj: | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 16(10) |
| ISSN: | 0884-0431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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