The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States

Abstract

Bone homeostasis is a dynamic equilibrium between bone-forming osteoblasts and bone-resorbing osteoclasts. This process is primarily controlled by the most abundant and mechanosensitive bone cells, osteocytes, that reside individually, within chambers of porous hydroxyapatite bone matrix. Recent studies have unveiled additional functional roles for osteocytes in directly contributing to local matrix regulation as well as systemic roles through endocrine functions by communicating with distant organs such as the kidney. Osteocyte function is governed largely by both biochemical signaling and the mechanical stimuli exerted on bone. Mechanical stimulation is required to maintain bone health whilst aging and reduced level of loading are known to result in bone loss. To date, both in vivo and in vitro approaches have been established to answer important questions such as the effect of mechanical stimuli, the mechanosensors involved, and the mechanosensitive signaling pathways in osteocytes. However, our understanding of osteocyte mechanotransduction has been limited due to the technical challenges of working with these cells since they are individually embedded within the hard hydroxyapatite bone matrix. This review highlights the current knowledge of the osteocyte functional role in maintaining bone health and the key regulatory pathways of these mechanosensitive cells. Finally, we elaborate on the current therapeutic opportunities offered by existing treatments and the potential for targeting osteocyte-directed signaling.

Subcanalicular Nanochannel Volume Is Inversely Correlated With Calcium Content in Human Cortical Bone

“…Further, human bone is a major reservoir for mineral as it contains more than 90% of the calcium in the human body. (6) A lacunocanalicular network (LCN), a system that hosts osteocytes and their cytoplasmic processes and consists of osteocyte lacunae interconnected by nanometersized channels (canaliculi), is well known for its essential role in facilitating mechanotransduction, (7,8) mineral homeostasis through perilacunar/canalicular remodeling, (9) and fluid and solute transport. (5,10) These characteristics of the LCN have been deduced in part from numerous electron microscopic, X-ray nanotomographic and confocal laser scanning microscopic, as well as other imaging techniques.…”

Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors

“…The convergence of mechanical and biological considerations, in addition to adequate vascular supply at the healing site and the physiological host state in the "diamond concept", conceptualizes a framework of fracture repair comparable to a polychemotherapy attack on non-unions. Within this context, the healing process is facilitated by osteoinductive mediators (cytokines released by macrophages), an underlying matrix (extracellular matrix promoting "homing" and migration of osteogenic cells), osteogenic cells (i.e., multipotent MSCs and committed osteoprogenitors from the adjacent periosteum), and mechanical stability (sensed by osteocytes) [143,144]. In addition, adequate blood supply is necessary (periosteal vascularization is essential for the influx of osteoprogenitors and association of invading blood vessels with osteoblast precursors) [145,146] and beneficial host factors (no smoking, cessation of harmful drugs) may be involved [11,22,23].…”

Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat

“…Additionally, evidence suggests that osteoblasts and their precursor cells are responsive to mechanical stimuli. [6][7][8][9] Furthermore, mechanical cues have been demonstrated to regulate various functions of bone cells, including proliferation, differentiation, and matrix formation. [10][11][12][13] Nevertheless, the molecular mechanisms by which osteoblasts and osteocytes recognize and process mechanical stimuli remain poorly understood.…”