Applying Proteomics to Study Crosstalk at the Cartilage-Subchondral Bone Interface in Osteoarthritis: Current Status and Future Directions

Osteoarthritis (OA) is the most common age-related degenerative joint disorder. It is considered a disease of the entire joint, which is not simply a result of attrition but rather abnormal remodelling and coalescent failure of multiple tissues. Despite the prevalence of OA, therapeutic strategies are currently limited to the treatment of pain and inflammation. New disease-modifying agents that slow progression and diagnostic biomarkers are urgently required. Given the lack of treatment options to repair degradation of articular cartilage, anti-resorptive agents and anabolics, such as bisphosphonates, are candidate treatments for OA (

). An optimal treatment for OA will likely target at least two joint tissues, yet the factors that govern the bone-cartilage interactions during pathogenesis remain largely unknown.

The bone-cartilage interface is an important synergistic unit consisting of the area between the deep layers of articular cartilage and the underlying subchondral bone (

). The close physical association between subchondral bone and cartilage allows interaction and suggests biochemical and molecular crosstalk may contribute to OA pathology (

). Crosstalk is elevated at the osteoarthritic bone-cartilage juncture due to osteochondral angiogenesis and bone remodelling (Fig. 1). Vascular invasion from bone into cartilage and development of microcracks and fissures provide pathways for communication (

). Alterations in either bone or cartilage can modulate signalling pathways including HIF-2α, OPG/RANK/RANKL, TGF-β and Wntβ-catenin; these pathways may alter homeostasis of neighbouring tissues and affect the function of the joint unit as a whole (

). The biomarker CTX-II has been detected at the bone-cartilage interface and is associated with osteophyte formation (

). It has also been suggested that changes in the uCTX-II level may reflect the functional bone-cartilage unit, indicating the importance of crosstalk in OA pathophysiology (

). The role of the crosstalk in the progression of OA requires additional investigation using genomics, epigenetics, proteomics and metabolomics approaches.