engleski

Alteration of newly-induced endochondral bone formation in adult mice without TNF receptor 1

Tumor necrosis factor (TNF)-alpha, a major proinflammatory cytokine, exerts its role on bone cells through two receptors (TNFR1 and TNFR2). TNFR1, but not TNFR2, is expressed by osteoblasts and its function in bone formation in vivo is not fully understood. We compared in vivo new bone formation in TNFR1-deficient (TNFR1 ko) mice and wild-type mice, using two models of bone formation: intramembranous osification following tibial marrow ablation and endochondral ossification induced by bone morphogenetic protein (BMP)-2. Intramembranous osteogenesis in TNFR1 ko mice did not differ from the wildtype mice either in histomorphometric parameters or mRNA expression of bone-related markers and inflammatory cytokines. During endochondral osteogenesis, TNFR1 ko mice formed more cartilage (at post-implantation day 9), followed by more bone and bone marrow (at day 12). mRNAs for BMP-2, -4 and -7 were increased during the endochondral differentiation sequence in TNFR1 ko mice. The expression of receptor activator of NF-kappaB ligand (RANKL) and receptor activator of NF-kappaB (RANK), as assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR), was also increased significantly during endochondral ossification in TNFR1 ko mice. In conclusion, signalling through the TNFR1 seems to be a negative regulator of new tissue formation during endochondral but not intramembranous osteogenesis in an adult organism. BMPs and RANKL and its receptor RANK may be involved in the change of local environment in the absence of TNFR1 signalling.

bone; mouse; osteoinduction; RANKL; TNF-alpha

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