The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells

Abstract

It is becoming increasingly clear that Mesenchymal Stem Cell (MSC) differentiation is regulated by mechanical signals. Mechanical forces generated intrinsically within the cell in response to its extracellular environment, and extrinsic mechanical signals imposed upon the cell by the extracellular environment, play a central role in determining MSC fate. This paper reviews chondrogenesis and osteogenesis during skeletogenesis, and then considers the role of mechanics in regulating limb development and regenerative events such as fracture repair. However, observing skeletal changes under altered loading conditions can only partially explain the role of mechanics in controlling MSC differentiation. Increasingly, understanding how epigenetic factors such as the mechanical environment regulate stem cell fate is undertaken using tightly controlled in vitro models. Factors such as bio-engineered surfaces, substrates and bioreactor systems are used to control the mechanical forces imposed upon, and generated within, MSCs. From these studies, a clearer picture of how osteogenesis and chondrogenesis of MSCs is regulated by mechanical signals is beginning to emerge. Understanding the response of MSCs to such regulatory factors is a key step towards understanding their role in disease and regeneration.3

The effects of dynamic loading on the intervertebral disc

“…MSCs can differentiate into various cell lineages, including adipocyte, osteoblast, chondrocyte, myoblast, and tenocyte [15,91]; it may thus be likely that MSCs can be differentiated into IVD-like cells for tissue engineering applications. MSC differentiation can be directed by different factors, such as growth factors, or more importantly by mechanical factors, including shear, tension, compressive strain and hydrostatic pressure, all depending on the local environment such as matrix stiffness and structural arrangement, and the resulting cell shape and morphology differences, pH, oxygen and nutrient supply [52,93]. [45,58,70,72,122,123] MSCs in the IVD environment…”

Mechanical stretch enhances COL2A1 expression on chromatin by inducing SOX9 nuclear translocalization in inner meniscus cells

“…[36][37][38] Human meniscal specimens appear to fail at higher strains with average values between 21 and 55% of maximum strains. 39 Inner meniscus cells lose their chondrogenic phenotypes with an in vitro culture procedure.…”

Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs

“…Therefore identifying expansion and differentiation conditions that promote a more chondrogenic phenotype is critical to enhancing their utility for cartilage tissue engineering applications. Differentiation conditions that have been shown to promote the chondrogenic potential of MSCs include a low oxygen (5%) microenvironment (Khan et al 2007;Buckley et al 2010a;Meyer et al 2010), various combinations of growth factors (Mastrogiacomo et al 2001;Sakimura et al 2006;Hennig et al 2007;Diekman et al 2010;Buxton et al 2011) and mechanical signals (Huang et al 2005;Mauck et al 2007;Huang et al 2010a;Huang et al 2010b;Kelly and Jacobs 2010;Li et al 2010; Thorpe et al 2010;Haugh et al 2011). …”