Mechanotransduction of stem cells for tendon repair

Abstract

Tendon is a mechanosensitive tissue that transmits force from muscle to bone. Physiological loading contributes to maintaining the homeostasis and adaptation of tendon, but aberrant loading may lead to injury or failed repair. It is shown that stem cells respond to mechanical loading and play an essential role in both acute and chronic injuries, as well as in tendon repair. In the process of mechanotransduction, mechanical loading is detected by mechanosensors that regulate cell differentiation and proliferation via several signaling pathways. In order to better understand the stem-cell response to mechanical stimulation and the potential mechanism of the tendon repair process, in this review, we summarize the source and role of endogenous and exogenous stem cells active in tendon repair, describe the mechanical response of stem cells, and finally, highlight the mechanotransduction process and underlying signaling pathways.

Keywords: Mechanical loading; Mechanotransduction; Stem cells; Tendon repair.

Figure 1

Process of mechanotransduction in stem cells for tendon repair. This figure describes various ways by which mechanical loading stimulates mechanosensors to emit mechanical signals that convert into biochemical signals, which, in turn, activate the rearrangement of cytoskeleton and activate genetic expression via various signaling pathways. Cell-cell communication transduces signals from one cell to another cell via gap junctions. GPRC: G protein-coupled receptor; GFR: Growth factor receptor.

Figure 2

Signaling pathways responding to mechanical stimuli applied to a cell. This figure describes how mechanosensors, such as G-protein coupled receptors, integrins, ion channels, and growth factor receptor, sense mechanical loading and activate a series of signaling pathways downstream, in turn promoting gene expression and/or cytoskeleton rearrangement in tendon repair. ECM: Extracellular matrix; ROR: Receptor tyrosine kinase-like orphan receptor; GPCRs: G-protein coupled receptors; GFRs: Growth factor receptor; JNK: c-Jun N-terminal kinase; ROCK: Rho-associated protein kinase; ERK: Extracellular signal-regulated kinase; YAP: Yes-associated protein; TAZ: PDZ-binding motif.