Myoblast-derived ADAMTS-like 2 promotes skeletal muscle regeneration after injury.

Skeletal muscle regeneration and functional recovery after minor injuries requires the activation of muscle-resident myogenic muscle stem cells (i.e. satellite cells) and their subsequent differentiation into myoblasts, myocytes, and ultimately myofibers.

Secreted ADAMTS-like proteins as regulators of connective tissue function.

The extracellular matrix (ECM) determines functional properties of connective tissues through structural components, such as collagens, elastic fibers, or proteoglycans. The ECM also instructs cell behavior through regulatory proteins, including proteases, growth factors, and matricellular proteins, which can be soluble or tethered to ECM scaffolds. The secreted a disintegrin and metalloproteinase with thrombospondin type 1 repeats/motifs-like (ADAMTSL) proteins constitute a family of regulatory ECM proteins that are related to ADAMTS proteases but lack their protease domains.

En route towards a personalized medicine approach: Innovative therapeutic modalities for connective tissue disorders.

Connective tissue disorders can be caused by pathogenic variants (mutations) in genes encoding extracellular matrix (ECM) proteins. Such disorders typically manifest during development or postnatal growth and result in significant morbidity and mortality. The development of curative treatments for connective tissue disorders is hampered in part by the inability of many mature connective tissues to efficiently regenerate.

Secreted ADAMTS-like 2 promotes myoblast differentiation by potentiating WNT signaling.

Myogenesis is the process that generates multinucleated contractile myofibers from muscle stem cells during skeletal muscle development and regeneration. Myogenesis is governed by myogenic regulatory transcription factors, including MYOD1. Here, we identified the secreted matricellular protein ADAMTS-like 2 (ADAMTSL2) as part of a Wnt-dependent positive feedback loop, which augmented or sustained MYOD1 expression and thus promoted myoblast differentiation.

Macromolecular crowding enhances fibrillin-1 deposition in the extracellular matrix.

Biochemical and biophysical factors need consideration when modelling in vivo cellular behaviour using in vitro cell culture systems. One underappreciated factor is the high concentration of macromolecules present in vivo, which is typically not simulated under standard cell culture conditions. This disparity is especially relevant when studying biochemical processes that govern extracellular matrix (ECM) deposition, which may be altered due to dilution of secreted macromolecules by the relatively large volumes of culture medium required for cell maintenance in vitro.