title: Moderate joint loading reduces degenerative actions of matrix metalloproteinases in the articular cartilage of mouse ulnae.
abstract: Joint loading is a recently developed loading modality, which can enhance bone formation and accelerate healing of bone fracture. Since mechanical stimulation alters expression of matrix metalloproteinases (MMPs) in chondrocytes, a question addressed herein was, does joint loading alter actions of MMPs in the articular cartilage? We hypothesized that expression and activity of MMPs are regulated in a load-intensity-dependent manner and that moderate load scan downregulates MMPs. To test this hypothesis, a mouse elbow-loading model was employed. In the articular cartilage of an ulna, the mRNA levels of a group of MMPs as well as their degenerative activities were determined. The result revealed that elbow loading altered the expression and activities of MMPs depending on its loading intensity. Collectively, the data in this study indicate that 0.2 and 0.5 N joint loading significantly reduced the expression of multiple MMPs, that is, MMP-1, MMP-3, MMP-8, and MMP-13, and overall activities of collagenases or gelatinases in articular cartilage, while higher loads increased the expression and activity of MMP-1 and MMP-13. Furthermore, moderate loads at 1 N elevated the mRNA level of CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), but higher loads at 4 N did not induce a detectable amount of CITED2 mRNA. Since CITED2 is known to mediate the downregulation of MMP-1 and MMP-13, the result indicates that joint loading at moderate intensity reduces MMP activities through potential induction of CITED2. MMPs such as MMP-1 and MMP-13 are predominant collagenases in the pathology of osteoarthritis. Therefore, joint loading could offer an interventional regimen for maintenance of joint tissues.
authors.affiliation: Leni and Peter W. May Department of Orthopedics, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Hui B
authors.initials: HB
authors.lastname: Sun
authors.forename: Liming
authors.initials: L
authors.lastname: Zhao
authors.forename: Shigeo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D002358:Cartilage, Articular / Q000201:enzymology*; D004551:Elbow Joint / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014457:Ulna / Q000502:physiology*; D016474:Weight-Bearing
chemical_list: C110087:Cited2 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D015534:Trans-Activators; D015675:Osteocalcin; D020782:Matrix Metalloproteinases