title: Leptin induces the apoptosis of chondrocytes in an in vitro model of osteoarthritis via the JAK2‑STAT3 signaling pathway.
abstract: Emerging data has suggested a high prevalence of osteoarthritis (OA) among obese people. As an important adipokine secreted by white adipose tissue, leptin may be a key mediator in the progression of OA. Leptin exerts a catabolic effect on OA cartilage by increasing the production of metalloproteinase (MMP) enzymes, and contributes to apoptosis in chondrocytes. The current study aimed to explore the role of leptin on the apoptosis of chondrocytes in OA, and its underlying mechanisms. In the in vitro model of OA used in the present study, administration of exogenous leptin induced the generation of reactive oxygen species (ROS) and apoptosis in chondrocytes. It has been demonstrated that leptin is associated with the pathogenesis of OA via the Janus kinase 2 (JAK2)‑signal transducer and activator of transcription 3 (STAT3) signaling pathway, and data gathered in the present study demonstrated that suppression of this signaling pathway using a JAK2 inhibitor, AG490, significantly ameliorated leptin‑induced apoptosis in damaged chondrocytes in vitro, and reduced the generation of ROS. Furthermore, the protein expression levels of MMP‑13 and B‑cell lymphoma 2‑associated X protein were downregulated in the AG490‑treated group. The results of the present study may provide insight into the underlying molecular mechanism by which leptin induces apoptosis in chondrocytes. These findings indicated the importance of leptin as a therapeutic target for the treatment of OA in the overweight population.
authors.affiliation: Department of Pediatric Orthopedics, Xin Hua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Zi Ming
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Xin Hua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Pediatric Orthopedics, Xin Hua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatric Orthopedics, Xin Hua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Pediatric Orthopedics, Xin Hua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Pediatric Orthopedics, Xin Hua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Fang Chun
authors.initials: FC
authors.lastname: Jin
authors.affiliation: Department of Pediatric Orthopedics, Xin Hua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sha
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020032:Tyrphostins / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020738:Leptin; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D051028:bcl-2-Associated X Protein; D053614:Janus Kinase 2; D053509:Matrix Metalloproteinase 13