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====Effects of activity on healing==== 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.<ref name="Wang, J. H. C. 2006"/> 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.<ref name="Sharma P. M"/> 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.<ref name="Wang, J. H. C. 2006"/>
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