Tendon disorders—tendinopathies—are the primary reason for musculoskeletal consultation in primary care and account for up to 30% of rheumatological consultations. Whilst the molecular pathophysiology of tendinopathy remains difficult to interpret the disease process involving repetitive stress, and cellular load provides important mechanistic insight into the area of heat shock proteins which spans many disease processes in the autoimmune community. Heat shock proteins, also called damage-associated molecular patterns (DAMPs), are rapidly released following nonprogrammed cell death, are key effectors of the innate immune system, and critically restore homeostasis by promoting the reconstruction of the effected tissue. Our investigations have highlighted a key role for HSPs in tendion disease which may ultimately affect tissue rescue mechanisms in tendon pathology. This paper aims to provide an overview of the biology of heat shock proteins in soft tissue and how these mediators may be important regulators of inflammatory mediators and matrix regulation in tendinopathy. 1. Introduction Primary disorders of tendons are common and account for a high proportion of referrals to rheumatologists and orthopaedic surgeons [1]. The most commonly involved tendons are the rotator cuff (particularly supraspinatus) in the shoulder, the forearm extensor (tennis elbow) and flexor tendons (golfers elbow) in the forearm, the patella tendon in the knee, the Achilles tendon in the lower leg, and the tibialis posterior tendon in the ankle and foot. The intrinsic pathogenetic mechanisms underlying the development of tendinopathies are largely unknown however proinflammatory cytokines, apoptosis, and mechanical stress have recently been functionally implicated in several model systems [2, 3]. Increasing evidence is emerging that repetitive tissue trauma and its associated damage in stromal tissues are recognized at the cell level via receptor-mediated detection of intracellular proteins released by necrotic cells [4]. The term “alarmin” is proposed to categorise such endogenous molecules that function to mobilise and activate immune cells after interaction with their specific receptors during host defence and tissue repair [4]. Heat shock proteins (HSPs), a type of stress molecules involved in protein folding, are implicated as important tissue alarmins [5]. HSP activation can directly affect both innate and adaptive immunity, although controversial studies and opinions exist in the field [6–8]. The innate immune responses induced by HSPs include cytokine and chemokine
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