Mechanotransduction in osteogenesis

Abstract

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: Bone Joint Res 2019;9(1):1–14.

Hyaluronan Synthases’ Expression and Activity Are Induced by Fluid Shear Stress in Bone Marrow-Derived Mesenchymal Stem Cells

“…Mechanotransduction is known to be important for the regulation of osteogenic differentiation of MSCs [ 53 ]; therefore, we took a closer look at the bone-related genes contributing to the overrepresented pathways shown in Figure 3 (GO:0071773, GO:0045669, GO:0031214, GO:0030282 and GO:0045778). Our analysis revealed 24 significantly upregulated genes ( Figure 5 A,B) with a log 2 -fold change higher than 2.…”

“…Commitment towards the osteogenic lineage in hMSCs can be achieved via mechanotransduction [ 53 ], applying various types of physical stimuli such as tension [ 67 ], compression [ 68 , 69 ] and fluid shear stress [ 70 ]. Although a variety of mechanosensors have been described for different bone cells, e.g., integrins and cadherins/β-catenin in osteoblasts [ 71 , 72 , 73 , 74 ], the aforementioned mechanoperception by the primary cilium is the key player in hMSCs [ 37 , 75 ], resulting in an extensive upregulation of the expression levels of PTGS2 and BMP2 .…”

Induction of Axonal Outgrowth in Mouse Hippocampal Neurons via Bacterial Magnetosomes

“…The mechanosensitivity of cells determines a specific response to mechanical stimulation. Mechanical stretch can modulate several different cellular functions, such as the electrical activity of cardiac muscle [1], osteogenesis [2], and the myogenic response of small arteries [3]. Although mechanosensitivity is essential to all cells, studies were mainly devoted to clarify signal mechanotransduction in those cells that play a fundamentally mechanical role.…”

Phenotypes, Developmental Basis, and Genetics of Pierre Robin Complex

“…Developmental consequences could occur due to cells sensing and reacting to their physical environment through mechanotransduction, which is the cellular process of translating mechanical forces into biochemical signals or into the activation of diverse signalling pathways [ 42 ], or through the differential reaction of specific cell types to a genetic variant. Studies of mechanotransduction have shown that many diseases result from modifications in the force transmissions among cellular components and tissues that can be traced to changes in extra cellular matrix mechanics, cytoskeleton dynamics, the mechanosensing process of the cell, or altered downstream signaling pathways [ 42 , 43 ]. In the case of PR, defects in mechanotransduction of the involved tissues could underlie one or all of the defects, or the genetic variants currently associated with PR-like diseases could be functionally related through a shared genetic network.…”