title: Adipokines induce catabolism of newly synthesized matrix in cartilage and meniscus tissues.
abstract: OBJECTIVE
  Altered synovial levels of various adipokines (factors secreted by fat as well as other tissues) have been associated with osteoarthritis (OA) onset and progression. However, the metabolic effects of adipokines on joint tissues, in particular the fibrocartilaginous menisci, are not well understood. This study investigated effects of several adipokines on release of recently synthesized extracellular matrix in bovine cartilage and meniscus tissue explants.
  
  
  METHODS
  After labeling newly synthesized proteins and sulfated glycosaminoglycans (sGAGs) with3H-proline and35S-sulfate, respectively; bovine cartilage and meniscus tissue explants were cultured for 6 days in basal medium (control) or media supplemented with adipokines (1 µg/ml of leptin, visfatin, adiponectin, or resistin) or 20 ng/ml interleukin-1 (IL-1). Release of radiolabel and sGAG to the media during culture and the final explant water, DNA, sGAG, and retained radiolabel were measured. Matrix metalloproteinase (MMP-2) and MMP-3 activities were assessed using gelatin and casein zymography, respectively.
  
  
  RESULTS
  Water and DNA contents were not significantly altered by any treatment. Visfatin, adiponectin, resistin, and IL-1 stimulated sGAG release from meniscus, whereas only IL-1 stimulated sGAG release from cartilage. Release of3H and35S was stimulated not only by resistin and IL-1 in meniscus but also by IL-1 in cartilage. Retained3H was unaltered by any treatment, while retained35S was reduced by visfatin, resistin, and IL-1 in meniscus and by only IL-1 in cartilage. Resistin and IL-1 elevated active MMP-2 and total MMP-3 in meniscus, whereas cartilage MMP-3 activity was elevated by only IL-1.
  
  
  CONCLUSIONS
  Resistin stimulated rapid and extensive catabolism of meniscus tissue, similar to IL-1, whereas adipokines minimally affected cartilage. Release of newly synthesized matrix was similar to overall release in both tissues. These observations provide further indications that meniscal tissue is more sensitive to pro-inflammatory factors than cartilage and also suggest further study of resistin's role in OA.
authors.affiliation: a Department of Mechanical Engineering , Stanford University , Stanford , CA , USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Nishimuta
authors.affiliation: a Department of Mechanical Engineering , Stanford University , Stanford , CA , USA.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Levenston
mesh_terms: D054392:Adipokines / Q000494:pharmacology*; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D000072600:Meniscus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D054392:Adipokines; D017077:Culture Media, Conditioned; D006025:Glycosaminoglycans; D020782:Matrix Metalloproteinases
keywords: Adipokines; cartilage; catabolism; meniscus; resistin