title: Metalloproteases and rotator cuff disease.
abstract: The molecular changes occurring in rotator cuff tears are still unknown, but much attention has been paid to better understand the role of matrix metalloproteinases (MMP) in the development of tendinopathy. These are potent enzymes that, once activated, can completely degrade all components of the connective tissue, modify the extracellular matrix (ECM), and mediatethe development of painful tendinopathy and tendon rupture. To control the local activity of activated proteinases, the same cells produce tissue inhibitors of metalloproteinases (TIMP) that bind to the enzymes and prevent degradation. The balance between the activities of MMPs and TIMPs regulates tendon remodeling, whereas an imbalance produces a collagen dis-regulation and disturbances intendons. ADAMs (a disintegrin and metalloproteinase) are cell membrane-linked enzymes with proteolytic and cell signaling functions. ADAMTSs (ADAM with thrombospondin motifs) are secreted into the circulation, and constitute a heterogenous family of proteases with both anabolic and catabolic functions. Biologic modulation of endogenous MMP activity to basal levels may reduce pathologic tissue degradation and favorably influence healing after rotator cuff repair. Further studies are needed to better define the mechanism of action, and whether these new strategies are safe and effective in larger models.
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Biomedico, University of Rome, Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Del Buono
authors.forename: Francesco
authors.initials: F
authors.lastname: Oliva
authors.forename: Umile Giuseppe
authors.initials: UG
authors.lastname: Longo
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rodeo
authors.forename: John
authors.initials: J
authors.lastname: Orchard
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Denaro
authors.forename: Nicola
authors.initials: N
authors.lastname: Maffulli
mesh_terms: D006801:Humans; D045726:Metalloproteases / Q000378:metabolism*; D018570:Risk Assessment; D017006:Rotator Cuff / Q000601:surgery; D000070636:Rotator Cuff Injuries; D012680:Sensitivity and Specificity; D052256:Tendinopathy / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D013708:Tendon Injuries / Q000201:enzymology* / Q000503:physiopathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D017211:Treatment Failure; D014945:Wound Healing / Q000502:physiology
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D045726:Metalloproteases