The extracellular matrix (ECM) is an intricate network that plays a fundamental role in various cellular functions such as proliferation, migration, polarity, and differentiation. It also plays a very important role in the muscle-tendon unit (MTU), a single structure characterized by a high degree of heterogeneity in both cellular populations and chemical and mechanical properties. It has been observed that the ECM regulates the correct assembly of the MTU and that the significant mechanical stresses to which the MTU is subjected, along with the associated risks of rupture, are regulated by membrane receptors through mechanosignaling and counteracted by an increase in the expression of various cytoskeletal proteins and ECM components.
Alterations of the MTU are present in several diseases, including muscular dystrophies and age-related tendinopathies, diseases characterized by dramatic and irreversible remodeling of the ECM. The ultimate goal of this project is to clarify the multiple mechanisms through which muscle and tendon influence each other in musculoskeletal diseases related to aging, through the study of mechanosignaling from the ECM to the nucleus and vice versa, with particular attention to the LINC complex and the signaling pathways associated with it, including PI3K/Akt/mTOR, TGFbeta, and Wnt/b-catenin. Furthermore, we will assess changes in nuclear shape and the structure of the nuclear lamina in response to mechanical stimulation at the MTU level.
