Phenotypic changes in proliferation, differentiation, and migration of chondrocytes: 3D in vitro models for joint wound healing

Abstract

We aim to establish a 3D model of cartilage wound healing, and explore the involvement of chondrocytes in its repair. To characterize chondrocyte involvement in wound healing, an in vitro 3D model composed of chondrocyte mixing with either type II/I collagen or type I collagen matrix was established. The "defects" measuring 5 mm in diameter were made on each collagen matrix-chondrocyte construct to mimic in vivo cartilage defects. The effects of basic fibroblast growth factor (bFGF) on chondrocytes migration and differentiation were studied. The migration and Glucosaminoglycan (GAG) synthesis of chondrocytes in the defect areas were observed by microscopy after Alcian-blue staining. In the presence of bFGF, GAG expression increased significantly when chondrocytes were cultured in type II/I collagen matrix compared to type I collagen matrix. However, mild GAG accumulation was also found when cells were cultured in either type I or type II/I collagens without bFGF. In a 3D model of cartilage wound healing, bFGF promote chondrocyte proliferation, migration and differentiation in the presence of type II/I collagen matrix, and showed potential to regulate wound healing. These wound healing models may provide feasible methods to explore various drugs prior to human trials.

Effects of insulin-like growth factor 1 and basic fibroblast growth factor on the morphology and proliferation of chondrocytes embedded in Matrigel in a microfluidic platform

“…The inability to actively degrade the dense matrix surrounding the cells prevented the chondrocytes from migrating, resulting in the formation of large aggregates of spherical-shaped cells through proliferation over the 14 days of study. Similarly, in a study by Tsai et al (41), chondrocytes embedded in collagen gel migrated <0.6 mm in distance after 14 days in the presence of bFGF. As the cell culture chamber of the microfluidic platform used in the present study was miniaturized (2 cm), the limited migration of the chondrocytes had a negligible impact on the results.…”

Intermittent hydrostatic pressure maintains and enhances the chondrogenic differentiation of cartilage progenitor cells cultivated in alginate beads

“…For cartilage repair, stem cell migration into the cartilage defect is critical to the repair process (Tsai et al . ; Lee et al . ).…”

Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1

“…Our present results, taken together, precisely indicate that Src-PLCγ1-ERK1/2 is one of the important signal transduction pathways in the processes of chondrocyte proliferation and matrix synthesis induced by periodic mechanical stress. It has come to light that chondrocyte proliferation and migration function as major determinants directly affecting the quality of tissue-engineered cartilage (5,38,39). Therefore, Src-PLCγ1-ERK1/2 is one of the crucial signaling pathways that improve the quality of tissue-engineered cartilage in two different aspects under conditions of periodic mechanical stress.…”