The role of osteocytes-specific molecular mechanism in regulation of mechanotransduction - A systematic review

Abstract

Background: Osteocytes, composing over 90% of bone cells, are well known for their mechanosensing abilities. Aged osteocytes with impaired morphology and function are less efficient in mechanotransduction which will disrupt bone turnover leading to osteoporosis. The aim of this systematic review is to delineate the mechanotransduction mechanism at different stages in order to explore potential target for therapeutic drugs.

Methods: A systematic literature search was performed in PubMed and Web of Science. Original animal, cell and clinical studies with available English full-text were included. Information was extracted from the included studies for review.

Results: The 26 studies included in this review provided evidence that mechanical loading are sensed by osteocytes via various sensing proteins and transduced to different signaling molecules which later initiate various biochemical responses. Studies have shown that osteocyte plasma membrane and cytoskeletons are emerging key players in initiating mechanotransduction. Bone regulating genes expressions are altered in response to load sensed by osteocytes, but the genes involved different signaling pathways and the spatiotemporal expression pattern had made mechanotransduction mechanism complicated. Most of the included studies described the important role of osteocytes in pathways that regulate mechanosensing and bone remodeling.

Conclusions: This systematic review provides an up-to-date insight to different steps of mechanotransduction. A better understanding of the mechanotransduction mechanism is beneficial in search of new potential treatment for osteoporotic patients. By delineating the unique morphology of osteocytes and their interconnected signaling network new targets can be discovered for drug development.

Translational potential of this article: This systematic review provides an up-to-date sequential overview and highlights the different osteocyte-related pathways and signaling molecules during mechanotransduction. This allows a better understanding of mechanotransduction for future development of new therapeutic interventions to treat patients with impaired mechanosensitivity.

Keywords: Mechanotransduction; Osteocyte; Osteoporosis; Systematic review.

Figure 1

Flow chart for selection process.

Figure 2

Overview of the role of osteocyte-specific molecules in mechanotransduction. Osteocytes are interconnected to form LCN that facilitates mechanotransduction. Pericellular matrix contributes to sensation of load-induced interstitial fluid flow. Cell processes and cilium are connected to cytoskeleton and the deformation of structure can initiate signals transmission. Gap junctions between cells are responsible for direct exchange of signaling molecules. Proteins located at the extension parts and membrane can mediate mechanotransduction through a few pathways. The expression of bone remodeling genes will be altered when adapting to the changes in mechanical environment.