From streaming‐potentials to shear stress: 25 years of bone cell mechanotransduction

Abstract

Mechanical loads are vital regulators of skeletal mass and architecture as evidenced by the increase in bone formation following the addition of exogenous loads and loss of bone mass following their removal. While our understanding of the molecular mechanisms by which bone cells perceive changes in their mechanical environment has increased rapidly in recent years, much remains to be learned. Here, we outline the effects of interstitial fluid flow, a potent biophysical signal induced by the deformation of skeletal tissue in response to applied loads, on bone cell behavior. We focus on the molecular mechanisms by which bone cells are hypothesized to perceive interstitial fluid flow, the cell signaling cascades activated by fluid flow, and the use of this signal in tissue engineering protocols. ß

Protein Kinase G and Focal Adhesion Kinase Converge on Src/Akt/β-Catenin Signaling Module in Osteoblast Mechanotransduction

“…Decreased mechanical loading due to prolonged immobilization, muscle paresis, or weightlessness in space causes bone loss, whereas increased loading promotes bone formation (1). Mechanical loading of bone increases interstitial fluid flow through the lacunar-canalicular system, and the resulting fluid shear stress (FSS) 4 stimulates osteocytes embedded in lacunae/canaliculi and osteoblasts lining bone surfaces, although both cell types are also subjected to other types of mechanical forces (1)(2)(3)(4). Osteoblasts and osteocytes translate the mechanical signal into biochemical responses, resulting in enhanced proliferation and survival, respectively (1,5).…”

Intraoperative measurement of bone electrical potential: a piece in the puzzle of understanding fracture healing

“…The role of the bone electrical potential, although disputed in some studies, should stay in focus of the fracture healing research 14,15 . More comprehensive understanding of the bone electrical potential, could improve fracture treatment.…”

Cells in 3D matrices under interstitial flow: Effects of extracellular matrix alignment on cell shear stress and drag forces

“…In vivo, these cues are typically a combination of biochemical (e.g. inflammatory factors such as TGF-b) and mechanical signals (Orr et al, 2006;MacKenna et al, 2000;Ingber, 2006;Rhee and Grinnell, 2007;Chiquet et al, 2009;Davies, 2009;Fritton and Weinbaum, 2009;Hahn and Schwartz, 2009;Riddle and Donahue, 2009). Matrix fiber alignment is seen in healing wounds (Tomasek et al, 2002) and other inflammatory environments, where interstitial flow (IF) is increased due to capillary hyperpermeability and immune cell infiltration.…”