title: Mechanotransduction and cartilage integrity.
abstract: Osteoarthritis (OA) is characterized by the breakdown of articular cartilage that is mediated in part by increased production of matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS), enzymes that degrade components of the cartilage extracellular matrix. Efforts to design synthetic inhibitors of MMPs/ADAMTS have only led to limited clinical success. In addition to pharmacologic therapies, physiologic joint loading is widely recommended as a nonpharmacologic approach to improve joint function in osteoarthritis. Clinical trials report that moderate levels of exercise exert beneficial effects, such as improvements in pain and physical function. Experimental studies demonstrate that mechanical loading mitigates joint destruction through the downregulation of MMPs/ADAMTS. However, the molecular mechanisms underlying these effects of physiologic loading on arthritic joints are not well understood. We review here the recent progress on mechanotransduction in articular joints, highlighting the mediators and pathways in the maintenance of cartilage integrity, especially in the prevention of cartilage degradation in OA.
authors.affiliation: Department of Orthopaedic Surgery Department of Radation Oncology Oncophysics Research Institute, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Leong
authors.forename: John A
authors.initials: JA
authors.lastname: Hardin
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Cobelli
authors.forename: Hui B
authors.initials: HB
authors.lastname: Sun
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016474:Weight-Bearing
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases