Mannose-6-Phosphate Reduces Expression of Transforming Growth Factor β and Receptors in Rabbit Flexor Tendon Tenocytes

Abstract

Transforming growth factor β (TGF-β) plays an important role in tendon healing and adhesion formation. Inhibiting expression of TGF-β and receptors might prevent adhesion after tendon injury and/or opening surgeries. Here, we aimed to examine the effects of mannose-6-phosphate (M6P), an inhibitor of TGF-β as a natural plant compound, on expression of TGF-β and receptors in tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes that were isolated from rabbit flexor toes. We enriched tendon sheath fibroblasts, epitenon tenocytes, as well as endotenon tenocytes from rabbit flexor tendons, and subsequently cultured these cell types individually. All 3 cell types were grouped into 2 groups randomly: the experiment group supplemented with M6P (the M6P Group), and the Control Group treated with vehicle. Expression of TGF-β and receptors was assessed with enzyme-linked immunosorbent assays. TGF-β1 expression in the mRNA level was also assessed by in situ hybridization and immunohistochemistry. Expression of TGF-β and receptors in the M6P Group was remarkably lower than that in the Control Group across all 3 cell types (P < 0.05). In the M6P Group, the expression ratio of TGF-β1 mRNA and the expression level of intracellular TGF-β1 mRNA in 3 cell types were significantly decreased than those in the Control Group (P < 0.05). Therefore, expression of TGF-β1 was significantly lower in all three types of tendon cell treated with M6P. Collectively, M6P is a negative regulator of TGF-β and receptors in cultured rabbit tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes.