Osteoblast role in osteoarthritis pathogenesis

Abstract

Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling, and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors, and other proteic molecules which are involved in osteoarthritis pathogenesis.

Keywords: bone; osteoarthritis; osteoblast.

Figure 1

RANKL expressed on osteoblast (OB) mediates a signal for osteoclast (OC) differentiation via binding RANK expressed on osteoclast progenitors (OCP) (a). OPG is a soluble decoy receptor for RANKL, which is involved in the competitive inhibition of RANK/RANKL link, thus avoiding RANK activation and the following osteoclast activation (b)

Figure 2

Wnt signaling: at the basal state, GSK3 and CK1 phoshorylate β‐catenin and induce its degradation in the cytosol (a); Wnt binding to LRP‐5/6 and frizzled promotes Dvl‐mediated inactivation of the Axin‐GSK3‐ CK1‐APC complex. Thus, β‐catenin degradation is blocked by avoiding its phosphorylation. Increased β‐catenin levels promote its traslocation into the nucleus, where it forms a complex with T cell factor (TCF) (b). Dvl, dishevelled; GSK3, Glycogen Synthase Kinase 3; CK1, Casein Kinase 1; APC, Adenomatous Polyposis Coli