Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines

Abstract

Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout (omentin-1 ^−/−) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α (TNF-α), we determined that recombinant omentin-1 reduces the production of pro-inflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the pro-inflammatory cytokines.

Osteoporosis: Fat-secreted protein guards against bone loss in mice

An anti-inflammatory molecule produced by fat tissue helps protect against bone loss in mouse model of osteoporosis. Researchers from China’s Central South University in Changsha, led by Hui Xie, examined whether omentin-1, a protein secreted by fat tissue recently implicated in the development of obesity and diabetes, might play a role in osteoporosis as well. In mice engineered to lack omentin-1, they observed more bone tissue destruction and increased numbers of bone-resorbing osteoclast cells than in normal, healthy animals. The researchers also administered exogenous omentin-1 to mice either with an overactive inflammatory molecule or experimentally induced to develop osteoporosis. In both cases, they found that the protein suppressed inflammation and guarded against bone loss. Omentin-1 thus provides promising therapeutic agent for preventing or treating inflammatory bone diseases such as osteoporosis.

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