title: Pro-Inflammatory Cytokines: New Potential Therapeutic Targets for Obesity-Related Bone Disorders.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041. China.|Collaborative Innivation Centre of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu. China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Collaborative Innivation Centre of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu. China.
authors.forename: Chengqi
authors.initials: C
authors.lastname: He
authors.affiliation: Collaborative Innivation Centre of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu. China.
authors.forename: Xijie
authors.initials: X
authors.lastname: Yu
mesh_terms: D050156:Adipogenesis / Q000276:immunology; D001842:Bone and Bones / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000276:immunology; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D010006:Osteoblasts / Q000276:immunology; D010010:Osteoclasts / Q000276:immunology; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: IL-6; TNF-α; bone metabolism; lipid metabolism; obesity; osteoporosis