Competing regulation of matrix biosynthesis by mechanical and IGF-1 signalling in elderly human articular cartilage in vitro

This study investigates the separate and combined effects of IGF-1 and mechanical loads on chondrocytes in elderly human femoral head articular cartilage. Full depth biopsies of articular cartilage were subjected to either no load, static or cyclic (2s on/2s off) loading in unconfined compression at a stress of 1 MPa for 48 h with or without IGF-1 (300 ng ml^-1). Chondrocyte biosynthetic activity was measured using ³⁵S-sulphate and ³H-leucine during the last 24 h of loading. IGF-1 alone increased the rates of isotope incorporation, by 80% for ³⁵S-SO₄ and 40% for ³H-leucine, whereas loading alone reduced matrix biosynthesis. Applying load (cyclic or static) in the presence of IGF-1 returned the incorporation rates to their unstimulated levels. This study suggests elderly human articular cartilage is responsive to stimulation by IGF-1 but mechanical factors seem to act sufficiently strongly in the opposite direction to cancel this response.