Treatment with recombinant human macrophage colony-stimulating factor resorbs blood clot and restores osteoclastogenesis in heterotopic bone induced by partially purified native bone morphogenetic protein in osteopetrotic (op/op) mice.
Native bone morphogenetic protein and associated noncollagenous proteins induced the formation of heterotopic bone in the hindquarter muscles of osteopetrotic (op/op) mice and those of their phenotypically normal littermates (+/?). In op/op mice, the heterotopic bone consisted of a disorganized, densely packed mixture of irregular calcified cartilage, osteoid, chondro-osteoid, and fibrous tissue. Injections of recombinant human macrophage colony-stimulating factor initiated bone resorption that began in the peripheral vascularized regions of the metaphyses and continued in central areas of uncalficified avascular chondro-osteoid. On vascularized surfaces, osteoclasts were stained with tartrate-resistant acid phosphatase. In op/op mice treated with macrophage colony-stimulating factor, the osteoclasts were small, with only two or three nuclei, and they did not exhibit tartrate-resistant acid phosphatase staining. In untreated op/op mice, surgical blood clots persisted in the heterotopic sites as late as 3 weeks after the operation, whereas in treated op/op mice, the blood clots were absorbed almost as rapidly as in normal mice. Histologically, recombinant human macrophage colony-stimulating factor restored normal macrophage functions: absorption and organization of blood clot, osteoclastogenesis, synthesis of tartrate-resistant acid phosphatase, bone remodeling, islands of myelopoiesis, and construction of an ossicle complete with a cortex and a medulla filled with functioning hematopoietic bone marrow.
Miyazawa
K
K
Department of Orthopaedic Surgery, School of Medicine, University of California-Los Angeles 90024, USA.
Urist
M R
MR
D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002214:Capsules; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006579:Heterozygote; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000098:blood supply / Q000601:surgery; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011859:Radiography; D011994:Recombinant Proteins / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D002214:Capsules; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor