Role of Sulf1A in Wnt1- and Wnt6-induced growth regulation and myoblast hyper-elongation

Sulf1A expression, which is a characteristic of embryonic muscle, is undetectable in mature muscle fibres and quiescent satellite cells, but is re-activated in vivo upon injury and in vitro following activation of satellite cells. Sulf1A is known to enhance canonical Wnt signalling, and its association with Wnt1-induced satellite cell proliferation in vitro in the present study further confirmed this. However, exogenous Wnt6 decreased satellite cell proliferation but promoted the adoption of a hyper-elongated cell morphology in myoblasts on isolated single fibres in culture. Such Wnt6-induced cellular hyper-elongation and inhibition of proliferation was found to be dependent upon Sulf1A, as treatment with Sulf1A neutralising antibodies abolished both these effects. This indicates that Sulf1A can regulate Wnt6 signalling and cellular differentiation in skeletal muscle.

:▸ Sulf1 regulates not only Wnt1 but also Wnt6 signalling. ▸ Wnt1 and Wnt6 play contrasting roles in skeletal muscle growth regulation. ▸ Reduction in Sulf1 activity level can reverse Wnt6-induced myogenic differentiation.