Chondrogenic differentiation potential of osteoarthritic chondrocytes and their possible use in matrix-associated autologous chondrocyte transplantation

IntroductionAutologous chondrocyte transplantation (ACT) is a routine technique to regenerate focal cartilage lesions. However, patients with osteoarthritis (OA) are lacking an fit long-lasting treatment alternative, partly by reason of it is not admitted if chondrocytes from OA patients obtain the equivalent chondrogenic differentiation embryonic as chondrocytes from donors not affected by OA. Methods: Articular chondrocytes from patients with OA undergoing complete knee replacement (Mankin Score >3, Ahlback Score >2) and from patients undergoing ACT, here referred to as normal donors (ND), were isolated applying protocols used for ACT. Their chondrogenic differentiation potential was evaluated both in high-density pellet and stockade (Hyaff-11) cultures by histological proteoglycan assessment (Bern Score) and immunohistochemistry for collagen types I and II. Chondrocytes cultured in monolayer and scaffolds were subjected to gene word profiling using genome-wide oligonucleotide microarrays. Signal counsel were verified by using real-time PCR. Results: Chondrocytes from ND and OA donors demonstrated accumulation of corresponding amounts of cartilage matrix components, including sulphated proteoglycans and collagen types I and II. The mRNA expression of cartilage markers (ACAN, COL2A1, COMP, CRTL1, SOX9) and genes involved in matrix synthesis (BGN, CILP2, COL9A2, COL11A1, TIMP4) was highly induced in 3D cultures of chondrocytes from both donor groups. Genes associated with hypertrophic or OA cartilage (ALPL, COL1A1, COL3A1, COL10A1, MMP13, POSTN, PTH1R, RUNX2) were not significantly regulated between the two groups of donors. The expression of 661 genes, including COMP, FN1, and SOX9, was differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished between the OA and ND chondrocytes, and by oneself 184 genes were differentially regulated. Conclusions: Matchless infrequent genes were differentially expressed between OA and ND chondrocytes in Hyaff-11 culture. The risk of differentiation into hypertrophic cartilage does not seem to be increased for OA chondrocytes. Our findings propose that the chondrogenic capacity is not significantly affected by OA, and OA chondrocytes fulfil the requirements for matrix-associated ACT.

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