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.

Mesenchymal stem cell-mediated endochondral ossification utilising micropellets and brief chondrogenic priming

“…On the contrary, a less dense matrix could be invaded more easily, leading to faster vascularisation and remodelling, thus resulting in quicker bone formation. Supporting our hypothesis, it has previously been shown that GAG depletion in articular cartilage leads to an increase in blood vessel invasion, which contributes to osteoarthritis and bone development in diseased cartilage (Akkiraju and Nohe, 2015;Connelly et al, 2008). However, we also hypothesised that a minimum level of matrix production was necessary for bone formation to occur and to prevent pellets from being resorbed or lost in vivo, as evidenced by the fact that 7 d primed pellets -that had extremely low levels of GAG production pre-implantation -were unable to (Fig.…”

Comparative Study on Cartilage Tissue Collected From Less- and Severely-Affected Region of Osteoarthritic Knee

“…This ECM acts as an absorbent and helps in load distribution throughout the joint surface. Disruption of the ECM balance caused from the damage of the articular surface collagen network is shown to significantly change the load bearing ability of the articular cartilage, and increase the chance to OA conditions (Akkiraju, & Nohe 2015;Setton et al 1994;Setton et al 1993). It results in progressive cartilage degradation characterized by the softening, fibrillation, and erosion of the articular surface (Sandell & Aigner 2001).…”

Biomaterials for Cartilage Tissue Engineering

“…It was reported that the in vitro expansion of these cells is limited because once removed from their extracellular environment and expanded in monolayer, chondrocytes would rapidly lose their differentiated phenotype. Recently, it was reported a solution for this problem, if these cells are suspending in a 3D environment like collagen gel, alginate beads and agarose gel the chondrocyte phenotype can be retained or re-expressed [5,49,50].…”