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

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

Volume: 18 Issue: 14

Author(s): Tiantian Wang, Chengqi He*Xijie Yu*

Affiliation:

• Rehabilitation Medicine Center, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu,China

• Laboratory of Endocrinology and Metabolism, Department of Endocrinology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu,China

Keywords: TNF-α, IL-6, bone metabolism, lipid metabolism, obesity, osteoporosis.

Abstract: 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.

Cite this article as:

Wang Tiantian , He Chengqi*, Yu Xijie *, Pro-Inflammatory Cytokines: New Potential Therapeutic Targets for Obesity-Related Bone Disorders, Current Drug Targets 2017; 18 (14) . https://dx.doi.org/10.2174/1389450118666170104153512