Prostaglandin E₂, collagenase, and cell death responses depend on cyclical load magnitude in an explant model of tendinopathy

Abstract

Tendinopathy is a significant clinical problem that can result from repetitive activity. While the precise etiology of this condition remains unclear, the cellular response to cyclical loading is believed to have a contributory role to the pathology of tendinopathy. This study examined the short-term biochemical response of avian flexor digitorum profundus tendon to repetitive cyclic loadings of varying magnitude. An in vitro tendon explant model was utilized to apply four levels of haversine tensile stress (peak stress of 0, 3, 12, and 18 MPa) at 1.0 Hz, 8 hr/day for 3 days. The 12 and 18 MPa levels were known to cause significant mechanical damage based on previous work. Tissue media was recovered and analyzed for prostaglandin E(2) (PGE(2)), lactate dehydrogenase (LDH, measure of cell death), and collagenase levels. Tissue samples were recovered and analyzed for cell viability, total collagen, and sulfated glycosaminoglycan content. Collagenase, LDH, and PGE(2) levels were found to be influenced by loading magnitude (p < 0.05) with higher levels being present at higher load magnitudes. Varying cyclical load magnitude caused minimal compositional changes as collagen content and glycosaminoglycan did not change. These results indicate that elevated cyclical mechanical loading of tendon quickly results in altered biochemical tissue responses indicative of tissue injury. More sustained cyclical loading over time may be required for these initial responses to induce more dramatic tissue changes as observed in clinical tendinopathy.

Identification of differentially expressed genes and small molecule drugs for the treatment of tendinopathy using microarray analysis

“…Consistent with the present findings, Riley (3) suggested that tendon matrix damage is the primary event, overwhelming the ability of the resident cell population to repair structural defects and degradation of the extracellular matrix may affect the structural properties of the tendon. Previous studies (27,28) have also reported that fibronectin is markedly increased following tendon injury when compared with the levels in the normal tendon and consequently has been implicated in cell adhesion, migration and differentiation at the site of injury. Therefore, the present study indicates that these integrin genes associated with focal adhesion have crucial roles in tendinopathy development.…”

Fascicles from energy-storing tendons show an age-specific response to cyclic fatigue loading

“…In this study, experiments were performed on tissues that had previously been frozen, and as such cell response could not be studied. However, it has previously been reported that cyclic loading of viable tendon explants in vitro results in increased cell death and production of prostaglandin-E2 and collagenases at high magnitudes of applied load [55]. rsif.royalsocietypublishing.org J. R. Soc.…”

Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

“…When the rotator cuff is torn, interleukin-1β (IL-1β) is produced in the torn tendon, stimulating cyclooxygenase 2 (COX-2) expression and subsequent prostaglandin E2 (PGE2) production [2]. In in vitro model systems, mechanical loading often don fibroblasts or isolated tendon increases PGE2 production and release [3,4,5]. Exogenous PGE2 treatment inhibits tendon fibroblast proliferation and collagen synthesis in vitro [6] and causes localized tendon disorganization and degeneration in vivo [7,8].…”