Role of Chondrocytes in Cartilage Formation, Progression of Osteoarthritis and Cartilage Regeneration

Abstract

Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration.

Keywords: articular cartilage; bone; chondrocytes; collagen; extracellular matrix; stem cells; synovial.

Figure 1

Organization of normal articular cartilage. Superficial, middle, and deep zones and their extracellular matrix is divided using different sections. Growth factors that control the chondrocyte function are divided based on the stage of chondrocyte lineage.

Figure 2

Signaling cascades involved in Osteoarthritis. Red arrows indicate the primary signaling protein that regulate OA progression. The black arrows signify the activation of the proteins. The bars indicate inhibition of the proteins.