Heparin augments osteoclast resorption-stimulating activity in serum

Area of Science:

• Bone biology
• Cell biology
• Pharmacology

Background:

• Mast cells and their granules, particularly heparin, are associated with increased bone resorption and osteoporosis.
• Long-term heparin administration is known to induce osteoporosis.

Purpose of the Study:

• To investigate the effect of heparin on osteoclast bone resorption.
• To identify the mechanism by which heparin influences osteoclast activity and bone resorption.

Main Methods:

• Osteoclasts were disaggregated from neonatal rat long bones.
• Osteoclast function was assessed in the presence and absence of serum and varying concentrations of heparin.
• The interaction of heparin with serum factors was examined to understand the mechanism of action.

Main Results:

• Heparin alone did not affect osteoclast function without serum.
• In the presence of serum (newborn calf, rat, or bovine), heparin (25-100 µg/ml) significantly increased osteoclastic bone resorption.
• Heparin enhanced a serum-derived osteoclast resorption-stimulating activity (ORSA), potentially a novel heparin-binding factor, as known heparin-binding proteins did not substitute for ORSA.
• The resorption-enhancing effect of glycosaminoglycans (GAGs) depended on sulfation and molecular weight; high molecular weight heparan sulfate, fucoidan, and dextran sulfate were effective, while low molecular weight heparin and chondroitin sulfates were not.

Conclusions:

• Heparin augments the activity of a serum factor that stimulates osteoclastic bone resorption.
• Mast cells or heparin therapy may increase bone resorption and contribute to osteoporosis by enhancing this heparin-binding factor.
• The findings suggest a novel mechanism for regulating osteoclastic bone resorption involving heparin and specific serum factors.