Bone–cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies

Abstract

Currently, osteoarthritis (OA) is considered a disease of the entire joint, which is not simply a process of wear and tear but rather abnormal remodelling and joint failure of an organ. The bone-cartilage interface is therefore a functioning synergistic unit, with a close physical association between subchondral bone and cartilage suggesting the existence of biochemical and molecular crosstalk across the OA interface. The crosstalk at the bone-cartilage interface may be elevated in OA in vivo and in vitro. Increased vascularisation and formation of microcracks associated with abnormal bone remodelling in joints during OA facilitate molecular transport from cartilage to bone and vice versa. Recent reports suggest that several critical signalling pathways and biological factors are key regulators and activate cellular and molecular processes in crosstalk among joint compartments. Therapeutic interventions including angiogenesis inhibitors, agonists/antagonists of molecules and drugs targeting bone remodelling are potential candidates for this interaction. This review summarised the premise for the presence of crosstalk in bone-cartilage interface as well as the current knowledge of the major signalling pathways and molecular interactions that regulate OA progression. A better understanding of crosstalk in bone-cartilage interface may lead to development of more effective strategies for treating OA patients.

Modulation of Synovial Fluid‐Derived Mesenchymal Stem Cells by Intra‐Articular and Intraosseous Platelet Rich Plasma Administration

“…It is reasonable to speculate that, by administering PRP directly into SB, the concurrent presence of platelet-secreted TGF- β 1 and VEGF as well as plasma growth factors such as IGF-I and HGF could have a modulatory effect on TGF- β signaling pathway [12, 43]. This might reduce the presence of MSCs and could likely be associated with the shrinking of fibroneurovascular tissue of OA SB, an explanation which parallels the antifibrotic mechanism already reported in several cell phenotypes [43, 44]. …”

Osteoarthritis of the hip joint in elderly patients is most commonly atrophic, with low parameters of acetabular dysplasia and possible involvement of osteoporosis

“…More effective curative results may be expected if the patients are limited to the atrophy type strongly influenced by osteoporosis. Microstructural damage to the subchondral bone induces inappropriate crosstalk between osteoblasts and chondrocytes [6–8]. It is probably important to begin treatment for osteoporosis before such events occur.…”

“…However, excessive bone resorption characteristic of osteoporosis has also been found to occur in the early stages of OA [3], drawing attention to the functional unit consisting of articular cartilage and subchondral bone [4]. Molecular crosstalk between cartilage and subchondral bone contributes to the pathogenesis of OA [5–8]. Microstructural damage to the subchondral bone and subsequent bone loss by increased remodeling is associated with the pathogenesis of early-stage OA [9, 10].…”

3-D Structural Changes in Subchondral Bone and the Effect of Bisphosphonate Intervention in Early Osteoarthritis

“…Previous studies have focused on the effects of OA on articular cartilage, although more recent studies have revealed that the changes in the periarticular bones also play a role in OA progression. Prevention of these gradual structural changes might help reduce the destruction of articular cartilage, thereby altering the progression of OA and resulting in new methods for preventing and treating OArelated inflammation (Clouet et al, 2009;Yan et al, 2014;Yuan et al, 2014). The effects of changes in the structural and mechanical properties of subchondral bone on the articular cartilage are recognized by many researchers.…”