Botulinum toxin type A relieves sternocleidomastoid muscle fibrosis in congenital muscular torticollis

Abstract Congenital muscular torticollis (CMT) is a neck deformity that involves shortening of sternocleidomastoid muscle (SCM) characterized by muscle atrophy and interstitial fibrosis. To investigate wheatear Botulinum toxin type A (BTA) has anti-fibrotic effects in CMT, we established acquired muscular torticollis that mimetics CMT in rabbit by intra-SCM injection of anhydrous alcohol. The treatment groups received BTA (2.5 units or 5 units) injection into the fibrotic SCM. The shortening and thickening of SCM were recorded by B-mode ultrasound. Changes in Col1A1, Fn, α-SMA expression were determined by immunohistochemistry. In vitro studies, TGF-β induced NIH3T3 fibroblasts were used to evaluate anti-fibrosis effect of BTA. Expression of the myofibroblast marker α-SMA and fibrosis markers Col1A1 and Fn were detected by Western blotting and quantitative RT-PCR. Our results showed that BTA injection attenuated shortening and thickening of fibrotic SCM. Elevated expression of Col1A1, Fn, α-SMA were confirmed in this fibrotic muscle model but reversed after BTA injection. Similar results observed in TGF-β induced NIH3T3 fibroblasts in both mRNA and protein levels. In conclusion, our results suggested that BTA could be a promising agent against SCM fibrosis in CMT through regulating fibroblast and inhibiting myofibroblast differentiation.