Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix

Abstract

The purpose of this study was to evaluate the role of TGF-β in regulating tendon extracellular matrix after acute exercise. Wistar rats exercised (n = 15) on a treadmill for four consecutive days (60 min/day) or maintained normal cage activity. After each exercise bout, the peritendinous space of each Achilles tendon was injected with a TGF-β receptor inhibitor or sham. Independent of group, tendons injected with inhibitor exhibited ~50% lower Smad 3 (Ser) (P < 0.05) and 2.5-fold greater ERK1/2 phosphorylation (P < 0.05) when compared with sham (P < 0.05). Injection of the inhibitor did not alter collagen content in either group (P > 0.05). In exercised rats, hydroxylyslpyridinoline content and collagen III expression were lower (P < 0.05) in tendons injected with inhibitor when compared with sham. In nonexercised rats, collagen I and lysyl oxidase (LOX) expression was lower (P < 0.05) in tendons injected with inhibitor when compared with sham. Decorin expression was not altered by inhibitor in either group (P > 0.05). On the basis of evaluation of hematoxylin and eosin (H&E) stained cross sections, cell numbers were not altered by inhibitor treatment in either group (P > 0.05). Evaluation of H&E-stained sections revealed no effect of inhibitor on collagen fibril morphology. In contrast, scores for regional variation in cellularity decreased in exercised rats (P < 0.05). No differences in fiber arrangement, structure, and nuclei form were noted in either group (P > 0.05). Our findings suggest that TGF-β signaling is necessary for the regulation of tendon cross-link formation, as well as collagen and LOX gene transcription in an exercise-dependent manner.

Postnatal mechanical loading drives adaptation of tissues primarily through modulation of the non-collagenous matrix

“…Finally, pathway analysis of our proteomic data highlighted TGF-β1 as a regulator of ECM organisation and functional adaptation, predicted to be upregulated following loading in the energy-storing tendon. TGF-β is a known regulator of proteoglycans and collagens in tendon ( Potter et al, 2017 ; Robbins et al, 1997 ), a role we also demonstrated here with regulation of major ECM proteins mRNA expression following TGFB1 knockdown and stimulation in equine tenocytes. Further, TGFB1 mRNA expression was upregulated in the highly loaded energy-storing tendon only, supporting the hypothesis that TGF-β1 regulation is specific to the energy-storing tendon and subsequently indicating that it may specifically be associated with loading.…”

Osteocalcin expressing cells from tendon sheaths in mice contribute to tendon repair by activating Hedgehog signaling

“…It is essential for the recruitment and maintenance of tendon progenitors for tendon formation ( Pryce et al, 2009 ). It also induces collagen formation and matrix remodeling during tendon healing ( Hou et al, 2009 ; Lu et al, 2017 ; Potter et al, 2017 ; Kayama et al, 2016 ). Thus, activation of Hh signaling plays at least two roles.…”

Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-α

“…TNF-a has been shown to both enhance and inhibit TGF-b in an organspecific context. 39,40 Because the relationship between TNF-a in TGF-b induction in the esophagus remains elusive and canonical TGF-b signaling 41,42 is known to stimulate LOX production, [43][44][45] we hypothesized that the TNF-a-rich EoE microenvironment can induce epithelial production of TGF-b 46,47 to further perpetuate LOX production. We stimulated EPC2-hTERT cells with TNFa and found increased expression of TGF-b (Fig 6, A).…”