Leptin Promotes the Expression of Pro-inflammatory Mediator Genes but Does Not Alter Osteoclastogenesis and Early Stage Differentiation of Osteoblasts.

Abstract

Leptin, a hormone secreted by adipose tissue, plays a pivotal role in maintaining energy metabolism and bone quality. Dysregulation of leptin can lead to the development of various pathological conditions. For example, the concentration of leptin is increased in individuals with obesity, and this increased concentration is positively correlated with higher bone mass. In addition, mice lacking leptin or the leptin receptor exhibit substantial bone loss, further highlighting the pivotal role of leptin in regulating bone metabolism. However, the precise mechanism through which leptin affects bone remodeling remains unclear. The present study investigated the effect of leptin on osteoclastogenesis and osteoblastogenesis. Osteoblasts derived from MC3T3-E1 cells and osteoclasts derived from RAW 264.7 cells were used. The findings revealed that leptin did not substantially affect osteoclastogenesis or osteoblastogenesis. Furthermore, leptin did not affect cell viability during osteoclast differentiation. The expression of inflammatory mediators was increased in differentiating RAW 264.7 cells. However, the expression of critical bone resorptive genes, including Ctsk and tartrate-resistant acid phosphatase, was not elevated following leptin stimulation. By contrast, leptin did not alter the expression of key osteogenic genes in preosteoblasts in the early stage of differentiation. These data demonstrate that leptin can stimulate the expression of pro-inflammatory mediators in differentiating osteoclasts. These changes do not affect osteoblastogenesis or osteoclastogenesis. Leptin may downregulate bone resorption and enhance mineralization to increase bone mass.