title: Upregulation of lipocalin-2 (LCN2) in osteoarthritic cartilage is not necessary for cartilage destruction in mice.
abstract: Lipocalin-2 (LCN2) is a recently characterized adipokine that is upregulated in chondrocytes treated with pro-inflammatory mediators and in the synovial fluid of osteoarthritis (OA) patients. Here, we explored the in vivo functions of LCN2 in OA cartilage destruction in mice.
  
  
  
  The expression levels of LCN2 were determined at the mRNA and protein levels in primary cultured mouse chondrocytes and in human and mouse OA cartilage. Experimental OA was induced in wild-type (WT) or Lcn2-knockout (KO) mice by destabilization of the medial meniscus (DMM) or intra-articular (IA) injection of adenoviruses expressing hypoxia-inducible factor (HIF)-2α (Ad-Epas1), ZIP8 (Ad-Zip8), or LCN2 (Ad-Lcn2). The effect of LCN2 overexpression on the cartilage of WT mice was examined by IA injection of Ad-Lcn2.
  
  
  
  LCN2 mRNA levels in chondrocytes were markedly increased by the pro-inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor-α (TNF-α), and by previously identified catabolic regulators of OA, such as HIF-2α and components of the zinc-ZIP8-MTF1 axis. LCN2 protein levels were also markedly increased in human OA cartilage and cartilage from various experimental mouse models of OA. However, overexpression of LCN2 in chondrocytes did not modulate the expression of cartilage matrix molecules or matrix-degrading enzymes. Furthermore, LCN2 overexpression in mouse cartilage via IA injection of Ad-Lcn2 did not cause OA pathogenesis, and Lcn2 KO mice showed no alteration in DMM-induced OA cartilage destruction.
  
  
  
  Our observations collectively suggest that upregulation of LCN2 in OA cartilage is not sufficient or necessary for OA cartilage destruction in mice.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
authors.forename: W-S
authors.initials: WS
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea. Electronic address: jschun@gist.ac.kr.
authors.forename: J-S
authors.initials: JS
authors.lastname: Chun
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism; D006801:Humans; D000071068:Lipocalin-2 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000071068:Lipocalin-2; C071332:Lcn2 protein, mouse
keywords: Chondrocytes; Lipocalin-2 (LCN2); Osteoarthritis