New Advances in Osteocyte Mechanotransduction

Abstract

Purpose of review: Skeletal adaptation to mechanical loading plays a critical role in bone growth and the maintenance of bone homeostasis. Osteocytes are postulated to serve as a hub orchestrating bone remodeling. The recent findings on the molecular mechanisms by which osteocytes sense mechanical loads and the downstream bone-forming factors are reviewed.

Recent findings: Calcium channels have been implicated in mechanotransduction in bone cells for a long time. Efforts have been made to identify a specific calcium channel mediating the skeletal response to mechanical loads. Recent studies have revealed that Piezo1, a mechanosensitive ion channel, is critical for normal bone growth and is essential for the skeletal response to mechanical loading. Identification of mechanosensors and their downstream effectors in mechanosensing bone cells is essential for new strategies to modulate regenerative responses and develop therapies to treat the bone loss related to disuse or advanced age.

Keywords: Bone; Mechanosensitive ion channel; Mechanotransduction; Osteocyte.

Figure 1.

Cell surface proteins and structures involved in osteocyte mechanotransduction. Wnt receptors including Lrp5, integrin-containing focal adhesions, primary cilia, voltage-gated calcium channels, and connexin-based gap junctions are the major mechanosensors being implicated in bone cells. Upon stimulation by mechanical loading, osteocytes promote osteoblast formation by increasing Wnt ligand expression and decreasing SOST expression. Mechanical stimulation also enhances osteocyte energy production by promoting mTOR signaling.