Elevated levels of osteoprotegerin (OPG) and hepatocyte growth factor (HGF) in rheumatoid arthritis

Rheumatic diseases are often associated with changes in bone metabolism. Ex cessive production and release of cytokines and other growth factors due to inflammation, e.g. tumor necrosis factor-alpha (TNF-alpha). receptor activ ator of NF-KB ligand (RANKL), interleukins such as IL-1 and IL-6. may cause alterations in bone homeostasis leading to bone degradation. Other compone nts such as osteoprotegerin (OPG) and possibly the ligand-receptor pair hep atocyte growth factor (HGF) and c-met may Counteract this destruction. We h ave measured the levels of OPG. and HGF.c-met, in serum, synovial fluid (SF ), and cartilage from patients with rheumatoid arthritis ( RA) and other ar thritides. We found a) elevated levels of both OPG and HGF in SF from RA pa tients relative to arthritides of other causes. b) increased levels of both OPG and HGF in SF From seropositive RA patients (RA +) compared to seroneg ative RA patients ( RA-), c) elevated levels of both OPG and HGF in serum f rom RA patients compared to healthy controls, d) no correlation between sev erity of inflammation and levels or OPG or HGF. and c) presence of HGF c-me t in both cartilage and synovial tissue. The most significant elevations of OPG and HGF were found in patients with RA, the rheumatic disease most fre quently associated with the development of secondary osteoporosis.