A role for TGF beta(1) in osteoclast differentiation and survival

Recently, tumour necrosis factor-related activation-induced cytokine (TRANC E) was shown to be necessary for osteoclast formation, We now report that T GF beta, a cytokine enriched in bone matrix, is also required, TCF beta not only powerfully synergized with TRANCE for induction of osteoclast-like ce lls (OCL) from bone marrow precursors and monocytes, but OCL formation was abolished by recombinant soluble TGF beta receptor II (TGF beta sRII), Prei ncubation in TGF beta was as effective as simultaneous incubation with TRAN CE, TGF beta-preincubation enhanced OCL formation at least partly by preven ting the development of resistance to OCL-induction that otherwise occurs w hen precursors are incubated in M-CSF. OCL formed in TRANCE also showed mor e rapid apoptosis than OCL in TRANCE plus TGF beta, Like TGF beta, incubati on on bone matrix prolonged and enhanced the sensitivity of precursors to O CL-induction by TRANCE, and this was reversed by TGF beta sRII, Taken toget her, this data is compelling evidence for a model in which TGF beta in matr ix or released from bone-lining or other cells maintains and enhances the o steoclast-forming potential of precursors as they migrate towards sites of cell-bound TRANCE. Thus, the specific circumstances necessary for osteoclas t formation and survival are TRANCE expression on osteoblastic cells and TG F beta in bone.