title: Leptin promotes apoptosis and inhibits autophagy of chondrocytes through upregulating lysyl oxidase-like 3 during osteoarthritis pathogenesis.
abstract: Leptin has been found highly expressed in human osteoarthritis. We aimed to explore the possible effects and mechanisms of leptin on the apoptosis and autophagy of chondrocytes during osteoarthritis pathogenesis.
  
  
  
  Gene expression profile from osteoarthritis affected and preserved cartilage were downloaded from NCBI's Gene Expression Omnibus database (GSE57218). Lysyl oxidase-like 3 (LOXL3) mRNA expression in cartilage tissues and leptin concentration in joint synovial fluid (SF) was measured in samples from 45 osteoarthritis patients and 25 healthy donors by real-time PCR and radioimmunoassay, respectively. Rat osteoarthritis model was induced by anterior cruciate ligament transection (ACLT). The expression of apoptosis regulators and autophagy markers were detected by Western blot. Cell survival and cell apoptosis were identified by CCK-8 and flow cytometry, respectively.
  
  
  
  Re-analysis on GSE57218 indicated that LOXL3 mRNA was upregulated in osteoarthritis affected cartilage. LOXL3 mRNA was upregulated in osteoarthritis patients, which was positively correlated with SF leptin concentration. Similar results were obtained in rat osteoarthritis model. Moreover, ACLT surgery led to a significant increase in the protein levels of cleaved caspase 3, and a notable decrease in the protein levels of Bcl-2, LC3 II/LC3 I and Beclin1. Silencing of LOXL3 in ACLT and leptin treated primary chondrocytes significantly inhibited cell apoptosis, and promoted cell proliferation and autophagy. Moreover, overexpression of LOXL3 remarkably inhibited autophagy of chondrocytes via activating mTORC1.
  
  
  
  LOXL3, a downstream of leptin, stimulated the apoptosis, but inhibited the autophagy of chondrocytes. LOXL3 is a potential therapy target for osteoarthritis.
authors.affiliation: Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, China; Department of Orthopaedic Surgery, Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, China; Zhejiang Chinese Medical University, China; Institute of Orthopaedics and Traumatology of Zhejiang Province, China.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Huang
authors.affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, China.
authors.forename: S H
authors.initials: SH
authors.lastname: Du
authors.affiliation: Zhejiang Chinese Medical University, China.
authors.forename: L G
authors.initials: LG
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Li
authors.affiliation: Zhejiang Chinese Medical University, China; Institute of Orthopaedics and Traumatology of Zhejiang Province, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, China.
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Zhejiang Chinese Medical University, China; Institute of Orthopaedics and Traumatology of Zhejiang Province, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, China. Electronic address: pjtongzj@sina.com.
authors.forename: P
authors.initials: P
authors.lastname: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002358:Cartilage, Articular; D019902:Chondrocytes; D006801:Humans; D020738:Leptin; D010003:Osteoarthritis; D008249:Protein-Lysine 6-Oxidase; D051381:Rats
chemical_list: D020738:Leptin; D008249:Protein-Lysine 6-Oxidase
keywords: Apoptosis; Autophagy; LOXL3; Leptin; Osteoarthritis