TNF-alpha and IL-1 beta suppress N-cadherin expression in MC3T3-E1 cells

Excessive production of tumor necrosis factor (TNF) and interleukin-1 (IL-1 ) secondary to estrogen deficiency have been implicated as the cause of ost eoporosis in postmenopausal woman. These cytokines appear to stimulate oste oclast precursor proliferation and activate mature osteoclast formation dir ectly and possibly indirectly via osteoblasts, To investigate the other pos sible roles that these cytokines may play in stimulating the bone resorptio n process, we examined the effect of TNF-alpha and IL-1 beta on cell-cell a dhesion molecules, cadherins, in osteoblastic MC3T3-E1 cells. In this study , we investigated cadherin expression and the effect of TNF-alpha, IL-1 bet a, and parathyroid hormone (PTH) on the expression of cadherins in MC3T3-E1 cells. Confluent cultures of MC3T3-E1 cells were challenged with recombina nt human TNF-alpha (1-100 U/ml), recombinant human IL-1 beta (1-100 ng/ml) and human PTH(1-34) (1-100 ng/ml), respectively. The results show that MC3T 3-E1 cells express functional cadherin molecules, N-cadherin and OB-cadheri n, TNF-alpha (10-100 U/ml) and IL-1 beta (10-100 ng/ml) suppressed N-cadher in without changing OB-cadherin expression, while PTH (1-100 ng/ml) had no effect on cadherin expression, These results raise the possibility that TNF -alpha and IL-1 beta may compromise the cell-cell adhesion of osteoblasts w hich cover the bone surface, The ensuing compromised cell-cell adhesion of osteoblasts may in turn facilitate the direct adhesion of osteoclasts on th e calcified bone matrix surface. These results implicate an indirect role f or osteoblasts in the promotion of bone resorption by TNF-alpha and IL-1 be ta.