Abstract
IntroductionArthritic bone loss in the joints of patients with rheumatoid arthritis is the result of a combination of osteoclastic bone resorption and osteoblastic bone formation. This process is not completely understood, and especially the importance of local inflammation needs further investigation. We evaluated how bone formation and bone resorption are altered in experimental autoimmune arthritis.MethodsTwenty-one female SKG mice were randomized to either an arthritis group or a control group. Tetracycline was used to identify mineralizing surfaces. After six weeks the right hind paws were embedded undecalcified in methylmethacrylate. The paws were cut exhaustively according to the principles of vertical sectioning and systematic sampling. 3D design-based methods were used to estimate the total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast-covered bone surfaces. In addition the presence of adjacent inflammation was ascertained.ResultsThe total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast covered surfaces were elevated in arthritic paws compared to normal paws. Mineralizing surfaces were elevated adjacent to as well as not adjacent to inflammation in arthritic mice compared to normal mice. In arthritic mice, eroded surfaces and osteoclast covered surfaces were larger on bone surfaces adjacent to inflammation than on bone surfaces without adjacent inflammation. However, we found no difference between mineralizing surfaces at bone surfaces with or without inflammation in arthritic mice.ConclusionsInflammation induced an increase in resorptive bone surfaces as well as formative bone surfaces. The bone formative response may be more general, since formative bone surfaces were also increased when not associated with inflammation. Thus, the bone loss may be the result of a substantial local bone resorption, which cannot be compensated by the increased local bone formation. These findings may be valuable for the development of new osteoblast targeting drugs in RA.
Highlights
Arthritic bone loss in the joints of patients with rheumatoid arthritis is the result of a combination of osteoclastic bone resorption and osteoblastic bone formation
The results demonstrate that the ratio between Oc.S and mineralizing surfaces (MS) was significantly larger on periosteal than on endosteal surfaces in arthritic mice (p,0.01) but not in control mice (p = 0.27)
In the present study we showed that the area of formative bone surfaces as well as the area of resorptive bone surfaces was higher in arthritic mice than normal mice
Summary
Arthritic bone loss in the joints of patients with rheumatoid arthritis is the result of a combination of osteoclastic bone resorption and osteoblastic bone formation. This process is not completely understood, and especially the importance of local inflammation needs further investigation. Osteoclasts and osteoblasts are the central cells in bone turnover, and the function of these two cell types is coupled in many ways, e.g. through receptor activator of nuclear factor kB ligand (RANKL), RANK ligand (RANKL), and osteoprotegerin (OPG) [3,4,5] How this coupling is disturbed in RA is not completely understood. The impact of inflammatory tissue on adjacent bone formation is interesting and needs further investigation
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