Osteoclast differentiation bone loss

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

If the RANKL/OPG system is a final effector on the biology of osteoclasts, then this system should be the basis for the antiresorptive effects of estrogen. Indeed, estrogen stimulates OPG synthesis for osteoblastic cells (Hofbauer et al. 1999), estrogen deficiency induced by OVX results in a decrease in OPG and increased RANKL production, an action that is prevented by estradiol administration, and OPG administration prevents bone loss induced by OVX (Simonet et al. 1997 Hofbauer et al. 2000 Hofbauer 1999). In addition, estrogen can suppress RANKL and M-CSF-induced differentiation of myelomonocytic precursors into multinucleated TRAP+ osteoclasts through an ER-dependent mechanism that does not require mediation by stromal cells (Shevde et al. 2000). Finally, treatment with estradiol inhibits the response of osteoclast precursors to the action of RANKL (Srivastava et al. 2001). 

SME both promoted osteoblast differentiation and inhibited osteoclast differentiation in vitro. Its ability to suppress bone loss has also been demonstrated in vivo. SME has been suggested to regulate bone turnover by influencing both osteoblasts and osteoclasts. These two effects are thought to involve other compounds. As these effects were associated with the methanol extract, the active components are thought to be nonpolar, low-molecular-weight molecules. It is expected that the active components will be identified in the near future. 

Osteoclast activation and mononuclear cell infiltration are generally associated with bone loss. The consumption of black tea effectively reduced osteoclast activation and oxidative stress mononuclear layer cells in rats, thus restoring skeletal health [121]. Osteoporosis is a familiar problem linked with chronic liver disease [122]. Tea compounds, including TFS and EGCG, suppressed the formation and differentiation of osteoclasts by decreasing their enz5miatic activities and the gene ex-... 

Calcitriol raises plasma calcium by activating osteoclasts to stimulate the mobilization of calcium from bone. It acts later to stimulate the laying down of new bone to replace the loss, by stimulating the differentiation and recruitment of osteoblast cells. 

---