Apelin plays a catabolic role on articular cartilage: in vivo and in vitro studies.
Adipokines play key roles in the regulation of bone growth, obesity, diabetes mellitus type 2, and HIV infection. As a newly discovered hormone in the adipokine family, the precise role of apelin on articular cartilage metabolism is not yet clear. The aim of this study was to evaluate the role of apelin on articular cartilage. In vitro, we examined the effects of apelin on normal chondrocyte proliferation and gene expression of metalloproteinases (MMPs) and interleukin-1beta (IL-1beta). In vivo, by intra-articular injection with apelin, we examined MMP-3, -9, collagen II and IL-1beta at both gene and protein levels. Furthermore, we measured the messenger RNA (mRNA) expression of ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) and the proteoglycan content in articular cartilage. Apelin stimulated the proliferation of chondrocytes and significantly increased mRNA levels of MMP-1, -3, -9 and IL-1beta in vitro. Intra-articular injection with apelin in vivo up-regulated the expression of MMP-3, -9, and IL-1beta as well as decreased the level of collagen II. Additionally, after treatment with apelin, mRNA levels of ADAMTS-4 and -5 markedly increased and depletion of proteoglycan in articular cartilage was found by histological assessment. These findings suggest that apelin plays a catabolic role in cartilage metabolism and is a risk factor in the pathophysiology of osteoarthritis.
Hu
Peng-Fei
PF
Department of Orthopedic Surgery, The Second Hospital of Medical College, Zhejiang University College of Medicine, Hangzhou, PR China.
Chen
Wei-Ping
WP
Tang
Jing-Li
JL
Bao
Jia-Peng
JP
Wu
Li-Dong
LD
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000073861:Apelin; D002352:Carrier Proteins / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000073861:Apelin; C498579:Apln protein, rat; D002352:Carrier Proteins; D024043:Collagen Type II; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D045726:Metalloproteases; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases