Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes
Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes
Osteoarthritis (OA) is a whole joint disease characterized by an important remodeling of the osteochondral junction. It includes cartilage mineralization due to chondrocyte hypertrophic differentiation and bone sclerosis. Here, we investigated whether gremlin-1 (Grem-1) and its BMP partners could be involved in the remodeling events of the osteochondral junction in OA. We found that Grem-1, BMP-2, and BMP-4 immunostaining was detected in chondrocytes from the deep layer of cartilage and in subchondral bone of knee OA patients, and was positively correlated with cartilage damage. ELISA assays showed that bone released more Grem-1 and BMP-4 than cartilage, which released more BMP-2. In vitro experiments evidenced that compression stimulated the expression and the release of Grem-1 and BMP-4 by osteoblasts. Grem-1 was also overexpressed during the prehypertrophic to hypertrophic differentiation of murine articular chondrocytes. Recombinant Grem-1 stimulated Mmp-3 and Mmp-13 expression in murine chondrocytes and osteoblasts, whereas recombinant BMP-4 stimulated the expression of genes associated with angiogenesis (Angptl4 and osteoclastogenesis (Rankl and Ccl2). In conclusion, Grem-1 and BMP-4, whose expression at the osteochondral junction increased with OA progression, may favor the pathological remodeling of the osteochondral junction by inducing a catabolic and tissue remodeling program in hypertrophic chondrocytes and osteoblasts.
- Sorbonne Paris Cité France
- Inserm France
- Sorbonne University France
- Assistance Publique -Hopitaux De Paris France
- SORBONNE UNIVERSITE France
Cartilage, Articular, [SDV]Life Sciences [q-bio], 610, Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Article, Mice, Chondrocytes, Osteogenesis, osteochondral remodeling, Matrix Metalloproteinase 13, Animals, Humans, gremlin-1; Bmp-4; osteochondral remodeling; mechanical stress; osteoarthritis; hypertrophic chondrocytes, Cell Proliferation, Bmp-4, gremlin-1, Osteoblasts, hypertrophic chondrocytes, mechanical stress, Cell Differentiation, Osteoarthritis, Knee, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, osteoarthritis, Intercellular Signaling Peptides and Proteins, Matrix Metalloproteinase 3, Chondrogenesis
Cartilage, Articular, [SDV]Life Sciences [q-bio], 610, Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Article, Mice, Chondrocytes, Osteogenesis, osteochondral remodeling, Matrix Metalloproteinase 13, Animals, Humans, gremlin-1; Bmp-4; osteochondral remodeling; mechanical stress; osteoarthritis; hypertrophic chondrocytes, Cell Proliferation, Bmp-4, gremlin-1, Osteoblasts, hypertrophic chondrocytes, mechanical stress, Cell Differentiation, Osteoarthritis, Knee, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, osteoarthritis, Intercellular Signaling Peptides and Proteins, Matrix Metalloproteinase 3, Chondrogenesis
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