The ECM-Cell Interaction of Cartilage Extracellular Matrix on Chondrocytes

Abstract

Cartilage extracellular matrix (ECM) is composed primarily of the network type II collagen (COLII) and an interlocking mesh of fibrous proteins and proteoglycans (PGs), hyaluronic acid (HA), and chondroitin sulfate (CS). Articular cartilage ECM plays a crucial role in regulating chondrocyte metabolism and functions, such as organized cytoskeleton through integrin-mediated signaling via cell-matrix interaction. Cell signaling through integrins regulates several chondrocyte functions, including differentiation, metabolism, matrix remodeling, responses to mechanical stimulation, and cell survival. The major signaling pathways that regulate chondrogenesis have been identified as wnt signal, nitric oxide (NO) signal, protein kinase C (PKC), and retinoic acid (RA) signal. Integrins are a large family of molecules that are central regulators in multicellular biology. They orchestrate cell-cell and cell-matrix adhesive interactions from embryonic development to mature tissue function. In this review, we emphasize the signaling molecule effect and the biomechanics effect of cartilage ECM on chondrogenesis.

Integrin signaling in cartilage development

“…This condensation is accompanied by initial chondrogenic differentiation triggered by Sox transcription factors Sox9, Sox5, and Sox6 (Akiyama et al 2002). Then, the condensed mesenchymal cells are further differentiated to chondroblasts which begin to secrete cartilage specific ECMs such as collagen type II (Gao et al 2014). At this moment, the chondroblast cells dissociate from each other and change their shape from fibroblast-like morphology to round-shaped cell.…”

“…During chondrogenesis, mesenchymal cells collectively migrate to the proper localization of the body and are tightly condensed to form the blueprint of future bone structures (Olsen et al 2000;Pietri et al 2004;Barna & Niswander 2007;Gao et al 2014) In this process, both cell-cell adhesion and cell-ECM interaction are the critical regulatory mechanisms for prechondrogenic gene expression (Oberlender & Tuan 1994;Tavella et al 1997;Bang et al 2000;DeLise & Tuan 2002). Shortly after, condensed mesenchymes proceed the differentiation program for characteristic chondrocyte lineages.…”

“…Shortly after, condensed mesenchymes proceed the differentiation program for characteristic chondrocyte lineages. During this process, the prechondrocyte begins to secrete cartilage specific ECM such as collagen type II and changes its morphology from the fibroblastlike cell to the round chondrocyte cell shape (Gao et al 2014). When the condensation process is completed, chondrocytes disintegrate and the collagen-based ECM networks fill the spaces to form cartilage tissues.…”

“…In addition to those ECMs, chondrocytes also secrete a huge amount of proteoglycans such as Aggrecan and chondroitin sulfates (Gao et al 2014). While the proteoglycans hold lots of water molecules to resist pressure and frictions, collagen-based matrices give tensile strength.…”

Effects of Bisphosphonate on the Expression of Matrix Enzymes during Endochondral Ossification

“…Physiological resorption of the cartilaginous matrix can be seen during endochondral bone formation in the epiphysis, a temporary cartilaginous structure. For substitution of this structure for bone, proteases in the matrix such as MMPs are of great importance, whereas cartilage-resorbing chondroclasts are secondary [18]. These proteases are produced by chondrocytes in a physiologic condition, whereas they are released from synoviocytes, and inflammatory cells in pathologic conditions such as osteoarthritis and rheumatoid arthritis [19].…”