IGF1 and osteosclerosis: In osteoarthritis, osteoblasts of the subchondral bone can produce large amounts of different types of IGF-1, while production of IGF-1 binding protein is reduced compared to normal subchondral bone (120), so large amounts of free IGF-1 promote bone reconstruction and lead to the development of osteosclerosis, which simultaneously exacerbates cartilage matrix degradation.