Musculoskeletal system-derived stem or progenitor cells, such as bone marrow-derived mesenchymal stem cells (BMSCs), cartilage stem or progenitor cells (CSPCs), and nucleus pulposus progenitor cells (NPPCs) are involved in the origin, development, regeneration, and many other physiological behaviors of musculoskeletal tissues. Noticeably, mechanical stimulation acts as an important extrinsic factor in regulating this process. As the major weight-bearing system, the musculoskeletal system was significantly influenced by various types of physiological forces (stretch, pressure, sheer flow, compression, stiffness). This mechanical stimulus-initiated molecular mechanotransduction has been intensively studied in various human and animal musculoskeletal tissues, such as cartilage, bone, muscle, tendons, and ligaments. For example, mechanical compression influences bone regeneration via regulating BMSCs differentiation, and there exists a physiological compression range for the NPPCs survival and intervertebral disc regeneration. It is evident that mechanosignaling plays a critical role in the genesis and maintenance of cellular and intracellular structures, and it is involved in many musculoskeletal diseases such as osteoporosis, osteoarthritis, and intervertebral disc degeneration.

Mechanotransduction in musculoskeletal tissues is a complex multiscale process. The extracellular matrix (ECM) network interacts simultaneously with many cells through adhesion receptors such as integrins or catherins at focal adhesion (FA) sites, which in turn structurally and functionally regulate cellular peripheral membrane proteins and their linkage to the cytoskeleton, including actin microfilaments, microtubules, and intermediate filaments. These events involve multimolecular biophysical events, complex biochemical reactions, as well as whole organelle responses such as the reorganization of the cytoskeleton, organelle biogenesis, fission-fusion of mitochondria or changes in shape and structure with consequences to organelle function. These dynamic cytoskeletal structures are connected to the ECM through FAs at the cell membrane, which in turn are exposed to external mechanical stimuli to which the organelles respond. Thus, mechanical forces affect the biological behaviours of the musculoskeletal systems via regulating both cellular fate commitment and ECM homeostasis.

The aim of this Special Issue is to solicit original research articles and review articles focusing on how mechanical forces are involved and regulate the biological functions of musculoskeletal stem/progenitor cells. We hope that this Special Issue will foster discussion between researchers about the mechanobiological factors in regulating musculoskeletal biological behaviour.

Potential topics include but are not limited to the following:

• Novel molecular mechanisms of mechanotransduction involved in the process of musculoskeletal cell death, senescence, injury, and repair
• Novel cellular models used for the study of mechanobiology, such as stretch, pressure, sheer flow, and compression-related cellular models
• Novel mechanisms of mechanical force-mediated cellular differentiation of musculoskeletal system derived stem or progenitor cells
• Novel candidates to promote musculoskeletal tissue repair and regeneration via regulating mechanosignaling pathways
• Novel biological scaffolds or techniques used for rebuilding mechanical stabilization of musculoskeletal tissues
• Novel biomaterials for musculoskeletal system regeneration or reconstruction
• Novel biomechanical sensors detectors
• Preclinical (in vitro and in vivo) evaluation of biomechanical properties of biomaterials/scaffolds in musculoskeletal tissue regeneration
• The association between mechanosignaling markers and musculoskeletal tissue regeneration
• Mechanobiology-associated tissue engineering strategies