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However, following surgery for rotator cuff repair, the four distinct zones disappear and the collagen fibers and other extracellular matrix proteins of the natural insertion form bridges.38 The tendon�Cbone healing of the rotator cuff is a complex process and requires many factors, including intrinsic and extrinsic cells, cytokines and growth factors, and collagens. The fibrillar type collagens, collagen I and collagen III, are critical in tendon�Cbone healing; collagen I is present during the remodeling, whereas collagen III is present MK-1775 in the early stage of the healing process and is associated with the degenerative and scar tissue.38 Healing failure is due, in part, to changes in the cartilage concentrations within the fibrovascular scar (composed of mostly type III collagen, which is replaced by type I collagen to achieve a specific ratio).3,39 Direct effect of vitamin D on the regulation of fibrocartilage in the four zones of the supraspinatus has not been examined. However, the effect of vitamin D on this healing process is to strengthen the postprocedural tendon-to-bone scar and, thus, increase the effectiveness of the healing.3 Investigators have found that vitamin D positively influences the rotator cuff tendons through MMPs (Figure 3). MMPs are enzymes that contain zinc ion in their active site and are essential in extracellular matrix CYTH4 breakdown and repair, specifically collagen degradation.18 Reider40 reported a correlation between increase in MMPs and poor healing in rotator cuff muscles.40 Likewise, blockade of MMPs in tendon-to-bone healing KU-55933 was shown to improve healing by increasing fibrocartilage and collagen organization as well as improving the scar strength in rats.39,41 An increase in MMP-1 and MMP-13 in rotator cuff synovial fluid correlates with decreased healing in the tendon-to-bone repair site. These MMPs signal for the degradation of collagen and connective tissue at the site of interest, an unfavorable phenomenon in rotator cuff healing.4,42 In a study of 35 participants, healing of the supraspinatus was shown to be inhibited by the presence of MMP-1 and MMP-9, with the defectively healed group possessing an increase of 2.5- and 5.2-fold, respectively, compared to that of the healed group (P=0.006 and P=0.021, respectively).4 TNF-�� stimulates the secretion of MMP-9 (P