Macro, Micro, and Molecular. Changes of the Osteochondral Interface in Osteoarthritis Development

Abstract

Osteoarthritis (OA) is a long-term condition that causes joint pain and reduced movement. Notably, the same pathways governing cell growth, death, and differentiation during the growth and development of the body are also common drivers of OA. The osteochondral interface is a vital structure located between hyaline cartilage and subchondral bone. It plays a critical role in maintaining the physical and biological function, conveying joint mechanical stress, maintaining chondral microenvironment, as well as crosstalk and substance exchange through the osteochondral unit. In this review, we summarized the progress in research concerning the area of osteochondral junction, including its pathophysiological changes, molecular interactions, and signaling pathways that are related to the ultrastructure change. Multiple potential treatment options were also discussed in this review. A thorough understanding of these biological changes and molecular mechanisms in the pathologic process will advance our understanding of OA progression, and inform the development of effective therapeutics targeting OA.

Keywords: cartilage; endochondral; hypertrophy; interaction; osteoarthritis; osteochondral junction.

FIGURE 1

Loss of integrity in the osteochondral interface in osteoarthritis. The illustration shows the process from a normal healthy joint turning into the end-stage OA joint. The normal knee joint (left top picture) showed the integrated image of the joint. The articular cartilage covers the contact interface between the two adjacent joint surfaces. Chondrocytes are aligned properly in the three layers. The collagen fibers are intact and robust, perpendicular to the surface in the osteochondral junction in the deep layer. The thin layer of the CCZ is located beneath the hyaline cartilage. Tidemark duplication is presented in the tidemark. The cement line is wavier than the tidemark. Subchondral bone is located under the calcified cartilage layer. The osteocyte network is intact. In the early stage of OA, Chondrocytes produce multiple kinds of inflammatory signals. Cartilage swelling or edema is also common in the early stage. Chondrocyte proliferation begins in this stage. The subchondral bone remodeling also begins in this stage, resulting in the increased porosity of the subchondral bone plate. With the disease progression, the neurovascular invade the osteochondral interface. The tidemark and cement line expresses more tortuosity than before. And gradually, the collagen network in the cartilage is disrupted. Calcified cartilage thinning is common in the mid-late stage. Bone cyst and osteophyte formation are also common in the stage. And at the end stage, total breakage of the cartilage fibrin is commonly found. Hypertrophic and apoptotic cells are universally seen in the area. The bony island is seen in the calcified cartilage. Vascular elements and nerves grow into the uncalcified cartilage zone. Apoptotic osteocytes and disruption of the osteocyte network are the main change in the subchondral bone plate.

FIGURE 2

Osteoarthritic cells express growth plate signals. The osteoarthritic chondrocytes express hypertrophic chondrocyte phenotype, which is commonly found in the growth plate of adolescents. The hypertrophic markers, including Col X, HIF-2α, Runx2, Osterix, and relevant hypertrophic genes are all altered in the process.