Abstract
The growth and differentiation factor 5 (GDF‐5) is known to play a key role in cartilage morphogenesis and homeostasis, and a single‐nucleotide polymorphism in its promoter sequence was found to be associated with osteoarthritis (OA). In addition, GDF‐5 was shown to promote extracellular matrix (ECM) production in healthy chondrocytes, to stimulate chondrogenesis of mesenchymal stem cells (MSCs) and to protect against OA progression in vivo. Therefore, GDF‐5 appears to be a promising treatment for osteoarthritis. However, GDF‐5 also promotes osteogenesis and hypertrophy, limiting its therapeutic utility. To circumvent this, a GDF‐5 mutant with lower hypertrophic and osteogenic properties was engineered: M1673. The present study aimed to evaluate and compare the effects of GDF‐5 and M1673 on primary porcine and human OA chondrocytes. We found that both GDF‐5 and M1673 can robustly stimulate ECM accumulation, type II collagen and aggrecan expression in porcine and human OA chondrocytes in 3D culture. In addition, both molecules also down‐regulated MMP13 and ADAMTS5 expression. These results suggest that M1673 retained the anabolic and anti‐catabolic effects of GDF‐5 on chondrocytes and is an alternative to GDF‐5 for osteoarthritis.
Highlights
Osteoarthritis (OA) is the most common joint disease worldwide and an important cause of disability for an increasing number of patients.[1]
We found that both growth and differentiation factor 5 (GDF-5) and M1673 can robustly stimulate extracellular matrix (ECM) accumulation, type II collagen and aggrecan expression in porcine and human OA chondrocytes in 3D culture
Both molecules down-regulated MMP13 and ADAMTS5 expression. These results suggest that M1673 retained the anabolic and anti-catabolic effects of GDF-5 on chondrocytes and is an alternative to GDF-5 for osteoarthritis
Summary
Osteoarthritis (OA) is the most common joint disease worldwide and an important cause of disability for an increasing number of patients.[1]. It was confirmed that M1673 stimulates chondrogenesis of MSCs to GDF-5 but has reduced hypertrophic and osteogenic properties.[17] The aim of the present study was to evaluate if the anabolic effect of GDF-5 on healthy chondrocytes observed by others is maintained in M1673 and to investigate the effect of both compounds on human OA chondrocytes. To achieve this objective, primary porcine chondrocytes and human OA chondrocytes from several donors were cultured in 3D with M1673 or GDF-5.
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