New findings in osteoarthritis pathogenesis: therapeutic implications

Abstract

This review focuses on the new perspectives which can provide insight into the crucial pathways that drive cartilage-bone physiopathology. In particular, we discuss the critical signaling and effector molecules that can activate cellular and molecular processes in both cartilage and bone cells and which may be relevant in cross talk among joint compartments: growth factors (bone morphogenetic proteins and transforming growth factor), hypoxia-related factors, cell-matrix interactions [discoidin domain receptor 2 (DDR2) and syndecan 4], signaling molecules [WNT, Hedgehog (Hh)]. With the continuous progression of our knowledge on the molecular pathways involved in cartilage and bone changes in osteoarthritis (OA), an increasing number of potentially effective candidates for OA therapy are already under scrutiny in clinical trials to ascertain their possible safe use in an attempt to identify molecules active in slowing or halting OA progression and reducing joint pain. We then review the principal molecules currently under clinical investigation.

Keywords: articular cartilage; new treatments; osteoarthritis; signaling pathways.

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

Figures

Figure 1.

Differences between normal and osteoarthritic (OA) joints. Normal: all relevant tissues are represented; OA: changes occurring in OA joint.

Figure 2.

Interplay of various signaling pathways acting upon the two main chondrocyte protagonist in osteoarthritis (OA) cartilage derangement and bone formation: fibrogenic chondrocyte and hypertrophic chondrocyte. ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; ALK, activin-like kinase; BMP, bone morphogenetic protein; Coll, collagen; DDR2, discoidin domain receptor 2; HIF, hypoxic inducible factor; IL, interleukin; MMP13, matrix metalloproteinase 13; RUNX2, Runt-related transcription factor 2; SMAD, small mother against decapentaplegic; SOX9, SRY-related high-mobility- group (HMG) box transcription factor 9; TGFβ, transforming growth factor β; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.