Defective binding of macrophages to bone in rodent osteomalacia and vitamin D deficiency. In vitro evidence for a cellular defect and altered saccharides in the bone matrix.
In the osteomalacic as well as normal skeleton, few osteoclasts are associated with osteoid-covered bone surfaces. The reason for this particular cellular deficit is not clear, but may relate to the inability of osteoclasts and/or osteoclast precursors (monocyte-macrophages) to attach to immature, unmineralized bone matrix, a step apparently essential for normal resorptive activity and osteoclast differentiation. In this study, we have examined cell-bone binding using macrophages (M phi) and bone isolated from vitamin D-deficient rats and hypophosphatemic, osteomalacic mice and from their normal counterparts. The data show that M phi-bone attachment is greatly reduced (P less than 0.001) in both vitamin D deficiency and hypophosphatemia, but that the mechanisms responsible for this reduction are apparently different in the two disorders. In hypophosphatemia, the reduction in binding appears solely attributable to the absence or inaccessibility of bone matrix oligosaccharides or glycoproteins essential to the attachment process. In vitamin D deficiency, on the other hand, not only is the bone matrix defective as a binding substrate, but the M phi, per se, is limited in its capacity to attach to normal, vitamin D-deficient, and hypophosphatemic bone.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D001857:Bone Matrix / Q000378:metabolism* / Q000473:pathology; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000494:pharmacology; D007015:Hypophosphatemia, Familial / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010018:Osteomalacia / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D014415:Tunicamycin / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism / Q000473:pathology*; D000509:alpha-Fetoproteins / Q000494:pharmacology
D002241:Carbohydrates; D000509:alpha-Fetoproteins; D014415:Tunicamycin