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Fibroblasts are one of the most abundant cell types in connective tissues. These cells are responsible for tissue homeostasis under normal physiological conditions. When tissues are injured, fibroblasts become activated and differentiate into myofibroblasts, which generate large contractions and actively produce extracellular matrix (ECM) proteins to facilitate wound closure. Both fibroblasts and myofibroblasts play a critical role in wound healing by generating traction and contractile forces, respectively, to enhance wound contraction. This review focuses on the mechanisms of force generation in fibroblasts and myofibroblasts and techniques for measuring such cellular forces. Such a topic was chosen specifically because of the dual effects that fibroblasts/myofibroblasts have in wound healing process— a suitable amount of force generation and matrix deposition is beneficial for wound healing; excessive force and matrix production, however, result in tissue scarring and even malfunction of repaired tissues. Therefore, understanding how forces are generated in these cells and knowing exactly how much force they produce may guide the development of optimal protocols for more effective treatment of tissue wounds in clinical settings.

The findings of this study suggest that PRP treatment of injured tendons is "safe" as it promotes TSC differentiation into tenocytes rather than nontenocytes, which would compromise the structure and function of healing tendons by formation of nontendinous tissues. Moreover, they suggest that PRP treatment can enhance tendon healing because tenocytes induced to differentiate by PRP are activated to proliferate quickly and produce abundant collagen to repair injured tendons that have lost cells and matrix.

While mechanical loading is known to be essential in maintaining tendon homeostasis, repetitive mechanical loading has also been implicated in the etiology of tendon overuse injuries. The purpose of this study was to determine whether cyclic mechanical stretching regulates inflammatory responses induced by interleukin-1β (IL-1β) treatment in human patellar tendon fibroblasts (HPTFs). HPTFs were grown in microgrooved silicone dishes, where they became elongated in shape and aligned with the microgrooves, which is similar to the shape and organization of tendon fibroblasts in vivo. Cyclic uniaxial stretching was then applied to silicone culture dishes with a 4% or 8% stretch at a stretching frequency of 0.5 Hz for a duration of 4 h in the presence or absence of 10 pM IL-1β treatment. Non-stretched cells in the presence or absence of IL-1β were used for controls, respectively. The expression of cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), and the production of prostaglandin E 2 (PGE 2 ) were measured. In the absence of stretching, it was found that 10 pM of IL-1β markedly induced higher levels of COX-2, MMP-1 gene expression, and PGE 2 production than non-treated cells. Furthermore, cells with 4% stretching decreased the COX-2 and MMP-1 gene expression and PGE 2 production that were stimulated by IL-1β, whereas cells with 8% stretching further increased these gene products and/or expression levels in addition to the effects of IL-1β stimulation. Thus, the results suggest that repetitive, small-magnitude stretching is antiinflammatory, whereas large-magnitude stretching is pro-inflammatory. Therefore, moderate exercise may be beneficial to reducing tendon inflammation.