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 proinflammatory
cytokines such as tumor necrosis factor-alpha (TNF-α) 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-α 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-α and IL-6 regulate bone metabolism
through the endocrine way. Several reports suggest that TNF-α 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-α 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-α and IL-6 in lipid and bone metabolisms.
We further discuss how TNF-α 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.