Involvement of COX inhibitor and arachidonic acid in manipulating obesity and obesity-induced bone resorption markers in obese mice.

Obesity and bone-loss have remained a focus of research. Obesity stimulates adipose tissue expansion and adipocyte hypertrophy, resulting in chronic low-grade inflammation in the adipocytes. This enlarged adipocyte secretes a variety of pro-inflammatory chemicals. Because of their endocrine signaling, these substances indirectly promote osteoclast activity and bone-loss. However, the role of COX-2 signaling in obesity-induced bone resorption gene expression has yet to be investigated. Thus, we conducted this study in the context of obesity, employing a high-fat diet-induced obese mouse model. Obese mice treated with a selective and non-selective COX-2 inhibitor (celecoxib and aspirin), significantly (p < 0.05) reduced adipogenic markers such as body and fat weight, serum lipids, mRNA expression of pro-inflammatory markers (COX-2, TNF-α, IL-6, and MCP-1) in adipose tissue and bone resorption markers (OPG, RANKL, Cathepsin K, and MMP-9) in tibia bone tissue. In addition, arachidonic acid (AA) supplementation significantly (p < 0.5) increased the expression of obesity-induced inflammatory cytokines in the tibia bone marrow via the COX-2-derived PGE2 signaling pathway, hence increase the osteoclastogenesis. These findings suggested that inhibiting the COX-2 signaling pathway could reduce obesity and inflammatory bone resorption. Although both the selective and non-selective COX inhibitors had similar effects, selective COX-2 was more effective in these events, indicating that COX-2 plays a critical role in obesity-associated inflammatory bone resorption.