<P> Matrix metalloproteinases (MMPs) have a very important role in the degradation and remodeling of the ECM during the healing process after a tendon injury . Certain MMPs including MMP - 1, MMP - 2, MMP - 8, MMP - 13, and MMP - 14 have collagenase activity, meaning that, unlike many other enzymes, they are capable of degrading collagen I fibrils . The degradation of the collagen fibrils by MMP - 1 along with the presence of denatured collagen are factors that are believed to cause weakening of the tendon ECM and an increase in the potential for another rupture to occur . In response to repeated mechanical loading or injury, cytokines may be released by tenocytes and can induce the release of MMPs, causing degradation of the ECM and leading to recurring injury and chronic tendinopathies . </P> <P> A variety of other molecules are involved in tendon repair and regeneration . There are five growth factors that have been shown to be significantly upregulated and active during tendon healing: insulin - like growth factor 1 (IGF - I), platelet - derived growth factor (PDGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF - β). These growth factors all have different roles during the healing process . IGF - 1 increases collagen and proteoglycan production during the first stage of inflammation, and PDGF is also present during the early stages after injury and promotes the synthesis of other growth factors along with the synthesis of DNA and the proliferation of tendon cells . The three isoforms of TGF - β (TGF - β1, TGF - β2, TGF - β3) are known to play a role in wound healing and scar formation . VEGF is well known to promote angiogenesis and to induce endothelial cell proliferation and migration, and VEGF mRNA has been shown to be expressed at the site of tendon injuries along with collagen I mRNA . Bone morphogenetic proteins (BMPs) are a subgroup of TGF - β superfamily that can induce bone and cartilage formation as well as tissue differentiation, and BMP - 12 specifically has been shown to influence formation and differentiation of tendon tissue and to promote fibrogenesis . </P> <P> In animal models, extensive studies have been conducted to investigate the effects of mechanical strain in the form of activity level on tendon injury and healing . While stretching can disrupt healing during the initial inflammatory phase, it has been shown that controlled movement of the tendons after about one week following an acute injury can help to promote the synthesis of collagen by the tenocytes, leading to increased tensile strength and diameter of the healed tendons and fewer adhesions than tendons that are immobilized . In chronic tendon injuries, mechanical loading has also been shown to stimulate fibroblast proliferation and collagen synthesis along with collagen realignment, all of which promote repair and remodeling . To further support the theory that movement and activity assist in tendon healing, it has been shown that immobilization of the tendons after injury often has a negative effect on healing . In rabbits, collagen fascicles that are immobilized have shown decreased tensile strength, and immobilization also results in lower amounts of water, proteoglycans, and collagen crosslinks in the tendons . </P> <P> Several mechanotransduction mechanisms have been proposed as reasons for the response of tenocytes to mechanical force that enable them to alter their gene expression, protein synthesis, and cell phenotype, and eventually cause changes in tendon structure . A major factor is mechanical deformation of the extracellular matrix, which can affect the actin cytoskeleton and therefore affect cell shape, motility, and function . Mechanical forces can be transmitted by focal adhesion sites, integrins, and cell - cell junctions . Changes in the actin cytoskeleton can activate integrins, which mediate "outside - in" and "inside - out" signaling between the cell and the matrix . G - proteins, which induce intracellular signaling cascades, may also be important, and ion channels are activated by stretching to allow ions such as calcium, sodium, or potassium to enter the cell . </P>

Where do tendons and ligaments receive their strength from