Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactions

Abstract

Chondrocyte differentiation is a multi-step process characterized by successive changes in cell morphology and gene expression. In addition to tight regulation by numerous soluble factors, these processes are controlled by adhesive events. During the early phase of the chondrocyte life cycle, cell-cell adhesion through molecules such as N-cadherin and neural cell adhesion molecule (N-CAM) is required for differentiation of mesenchymal precursor cells to chondrocytes. At later stages, for example in growth plate chondrocytes, adhesion signaling from extracellular matrix (ECM) proteins through integrins and other ECM receptors such as the discoidin domain receptor (DDR) 2 (a collagen receptor) and Annexin V is necessary for normal chondrocyte proliferation and hypertrophy. Cell-matrix interactions are also important for chondrogenesis, for example through the activity of CD44, a receptor for Hyaluronan and collagens. The roles of several signaling molecules involved in adhesive signaling, such as integrin-linked kinase (ILK) and Rho GTPases, during chondrocyte differentiation are beginning to be understood, and the actin cytoskeleton has been identified as a common target of these adhesive pathways. Complete elucidation of the pathways connecting adhesion receptors to downstream effectors and the mechanisms integrating adhesion signaling with growth factor-and hormone-induced pathways is required for a better understanding of physiological and pathological skeletal development.

Alleviating Effects of AS1892802, a Rho Kinase Inhibitor, on Osteoarthritic Disorders in Rodents

“…Beier et al reported that RhoA/Rock signaling suppresses chondrogenesis through the control of Sox9 expression and actin organization (33). Rho-ROCK signal transduction is involved in inhibition of chondrocyte differentiation as well as modulation of chondrocyte metabolism (34). Our data showing enhancement of proteoglycan staining in ATDC5 cells treated with AS1892802 supports their results.…”

Inducible nitric oxide synthase–nitric oxide signaling mediates the mitogenic activity of Rac1 during endochondral bone growth

“…Studies by our group and others have shown that Rho GTPases are important regulators of chondrocyte proliferation and differentiation (Kerr et al, 2008;Kumar and Lassar, 2009;Wang and Beier, 2005;Wang et al, 2004;Woods and Beier, 2006;Woods et al, 2009b;Woods et al, 2005;Woods et al, 2007a;Woods et al, 2007b). Rho family GTPases act as molecular switches that become activated in response to specific extracellular stimuli, including growth factors and integrin ligands, through the activity of guanine nucleotide exchange factors that exchange GTP for GDP (Heasman and Ridley, 2008;Vega and Ridley, 2007;Vega and Ridley, 2008).…”

“…Activated, GTPbound Rho proteins then interact with a large variety of downstream effectors, including cytoskeletal regulators and various kinases, to control a number of cellular events such as cell migration, cell cycle progression and gene expression. During the early steps of chondrogenesis, regulation of actin dynamics and cellular morphology appear to mediate many of the effects of Rho GTPases (Beier and Loeser, 2010;Woods and Beier, 2006;Woods et al, 2005;Woods et al, 2007a). However, additional mediators are probably involved in these activities of Rho GTPAses, in particular after cells have differentiated into chondrocytes.…”

Distribution of BDNF and TrkB isoforms in growing antler tissues of red deer

“…Then, the transcription of truncated isoform may be related to rearrangement of the actin cytoskeleton and subsequent morphological changes as observed in glial cells (Ohira et al, 2006(Ohira et al, , 2007 through a BDNF-independent pathway. In fact, it is known that Rho GTPases are of particular interest in chondrocytes because of their role in connecting signals from the extracellular matrix to the actin cytoskeleton and cellular morphology, which in turn can control cellular activities, such as cell cycle progression and gene expression (Woods et al, 2007).…”