TGF-β-induced SOCS3 expression augments TNF-α-induced osteoclast formation

• Published in: Biochemical and biophysical research communications Vol. 309; no. 4; pp. 762 - 767
• Main Authors: Lovibond, Alison C, Haque, S.Jaharul, Chambers, Timothy J, Fox, Simon W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-10-2003
• Subjects: Animals; Base Sequence; DNA Primers; Gene Expression Regulation - physiology; Interferon-beta - antagonists & inhibitors; Interleukin-10 - antagonists & inhibitors; Lineage-commitment; Male; Mice; Osteoclast; Osteoclasts - cytology; Proteins - genetics; Repressor Proteins; RNA, Messenger - genetics; SOCS3; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; TGF-β; TNF-α; Transcription Factors; Transforming Growth Factor beta - physiology; Tumor Necrosis Factor-alpha - physiology; SOCS3; TGF-β; Osteoclast; TNF-α; Lineage-commitment
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.08.068

Osteoclast differentiation is dependent on TGF-β to prime precursors to the osteoclast lineage. The mechanism by which TGF-β enables osteoclast formation is unknown. One possibility is that TGF-β opposes pro-inflammatory JAK/STAT signalling. Recently, we showed that TGF-β-induces SOCS3, an inhibitor of the JAK/STAT pathway, in precursors and enhances SOCS3 in RANKL-induced osteoclasts. We therefore elected to test the role of SOCS3 in the effect of other regulators of osteoclastic differentiation. We found that TNF-α-induced osteoclasts also express SOCS3 and TGF-β strongly up-regulates this. Moreover, TNF-α-induced osteoclast differentiation and total resorbed bone area were enhanced in SOCS3-retrovirally infected precursors, whereas antisense knockdown of SOCS3 suppressed formation and the augmentative effect of TGF-β. Furthermore, SOCS3 overexpression blunted the anti-osteoclastic effect of IFN-β but not IL-10. This suggests that TGF-β-induced expression of SOCS3 may represent a crucial mechanism by which TGF-β antagonizes specific anti-osteoclastic JAK/STAT signals, priming precursors for resorption rather than inflammatory functions.