Biochemical Signals Mediate the Crosstalk between Cartilage and Bone in Osteoarthritis.

Xuchang Zhou,Wei Wu,Yu Yuan,Hong Cao

doi:10.1155/2020/5720360

Xuchang Zhou, Wei Wu + Show 2 more

Open Access

https://doi.org/10.1155/2020/5720360

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Abstract

Osteochondral junction is a functional unit comprising the articular cartilage, calcified cartilage, and subchondral bone. Alteration in any component of this composite unit can disrupt the joint integrity and function directly or indirectly. Biochemical signals mediate the crosstalk between tissues and play an essential role in the initiation and progression of osteoarthritis. As osteoarthritis progresses, abnormal subchondral bone remodelling leads to increased angiogenesis and porosity of the subchondral bone plate, which further triggers biochemical signals to mediate the crosstalk between cartilage and bone, contributing to the progression of osteoarthritis. Notably, common biochemical signals include the TGF-β/Smad, Wnt/β-catenin, RANK/RANKL/OPG, and MAPK pathways. This biomarker crosstalk network is the basis of osteoarthritis pathogenesis, and some of their key regulators may be potential therapeutic targets for osteoarthritis drug therapy. This review summarised the biochemical crosstalk between cartilage and bone in the pathogenesis of osteoarthritis, which may provide the basis for the discovery of osteoarthritis treatment targets.

Highlights

Osteoarthritis (OA) is widely accepted as a common degenerative joint disease affected by biomechanics and biochemical signals, involving the entire joint, including the overlying articular cartilage (AC), the calcified cartilage (CC), and the underlying subchondral bone (SB)
Signals from OA subchondral osteoblasts in vitro stimulate the expression of ADAMTS-4, ADAMTS-5, matrix metalloproteinase- (MMP-)2, MMP-3, and MMP-9 in chondrocytes, whereas OA chondrocytes increase the activities of MMP-1 and MMP-2 in osteoblasts, which is mediated by phosphorylating the ERK1/2 signalling pathway [24], indicating that there may be a catabolism-related bidirectional crosstalk in the osteochondral junction during OA progression
OA is a multifactorial degenerative whole joint disease that results in a complex pathogenesis

Summary

Introduction

Osteoarthritis (OA) is widely accepted as a common degenerative joint disease affected by biomechanics and biochemical signals, involving the entire joint, including the overlying articular cartilage (AC), the calcified cartilage (CC), and the underlying subchondral bone (SB). OA is characterised by various phenotypes such as cartilage degeneration and calcification, synovial inflammation, osteophyte formation, vascular invasion, subchondral remodelling, and increased porosity in the subchondral bone plate (SBP) [1, 2]. Numerous studies have been conducted on the pathogenesis and treatment of OA, there are no effective strategies to reverse or block the progressive destruction of cartilage and periarticular bone in OA [3]. Recent studies have shown that there is molecular crosstalk between cartilage and SB contributing to OA pathology by increasing microcracks, vascular channels, and porosity of SB [8,9,10].

The Cartilage-Bone Unit

Biochemical Crosstalk in the Cartilage-Bone Unit

MAPK Signalling Pathways

The Potential Therapeutic Strategies Based on the Biochemical Crosstalk in OA

Findings

10. Conclusions