Pro-Inflammatory Cytokines: New Potential Therapeutic Targets for Obesity-Related Bone Disorders

Background: Obesity was traditionally considered as a positive regulator on the strength of bone. With the in-depth study, obesity is considered as a major risk factor for osteoporosis. Some pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are the factors that fat uses to negatively regulate bone metabolism. Objective: This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of pro-inflammatory cytokines for the treatment of obesity-related bone disorders. Results: Obese people and animals show a higher level of serum TNF-alpha and IL-6, which are produced by macrophages derived from adipose tissue. These pro-inflammatory cytokines regulate the proliferation and apoptosis of adipocyte, promote lipolysis, inhibit lipid synthesis and decrease blood lipids through autocrine and paracrine way. On the other hand, TNF-alpha and IL-6 regulate bone metabolism through the endocrine way. Several reports suggest that TNF-alpha is a negative regulator of osteoblast at some stages of differentiation and positively regulates osteoclast proliferation and differentiation. In contrast, IL-6 influences osteoblasts and osteoclasts through complex mechanisms, which reflect dual effects. In addition, TNF-alpha and IL-6 may regulate bone metabolism indirectly by regulating adiponectin and leptin released from adipocytes. Conclusion: In this review, we first summarize the role of TNF-alpha and IL-6 in lipid and bone metabolisms. We further discuss how TNF-alpha and IL-6 regulate the communication between fat and bone, and their pathological roles in obesity-related bone disorders. Lastly, we discuss the possibility of using pro-inflammatory signaling pathway as a therapeutic target to develop drug for obesity-related bone disorders.