Heparin augments osteoclast resorption-stimulating activity in serum.
Increased numbers of mast cells are commonly seen at sites of increased bone resorption and in osteoporosis. Long-term administration of heparin, a major component of mast cell granules, causes osteoporosis. We therefore tested the effect of heparin on bone resorption by osteoclasts disaggregated from neonatal rat long bones. We found that, in the absence of serum, heparin was without effect on osteoclast function. However, in the presence of newborn calf serum, rat serum, or bovine platelet-poor plasma-derived serum, heparin, in the range 25-100 micrograms/ml, induced an increase in osteoclastic bone resorption. Heparin appeared to act through binding and enhancement of an osteoclast resorption-stimulating activity (ORSA) present in serum. A number of known factors that show an affinity for heparin, including transforming growth factor-beta, platelet-derived growth factors, insulin-like growth factors I or II, acidic or basic fibroblast growth factors, fibronectin, or laminin, could not substitute for ORSA, suggesting that the activity may represent a novel heparin-binding factor. The ability of glycosaminoglycans (GAGs) and related molecules to enhance resorption was dependent on the degree of sulfation and on their size: The high molecular weight GAG heparan sulfate and polysaccharides fucoidan or dextran sulfate showed a similar effect, while low molecular weight heparin, chondroitin-2-sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate were without effect. We propose that mast cells or heparin therapy increases bone resorption through augmentation of the activity of a factor involved in the local and systemic regulation of osteoclastic bone resorption.
Fuller
K
K
Department of Pathology, St George's Hospital Medical School, London, England.
Chambers
T J
TJ
Gallagher
A C
AC
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption; D002478:Cells, Cultured; D006493:Heparin / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D006493:Heparin