Granulocyte/macrophage colony-stimulating factor and interleukin-3 correct osteopetrosis in mice with osteopetrosis mutation.

Abstract

Although young mice homozygous for the osteopetrosis (op) mutation usually developed prominent osteopetrosis, its severity was markedly reduced in aged op/op mice. This age-associated reversal of osteopetrosis was accompanied by the expansion of bone marrow cavities and increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive cells and of macrophages in the bone marrow. The TRAP-positive cells were mononuclear and developed ruffled borders and numerous vesicles, vacuoles, and granules. Enzyme-linked immunosorbent assay demonstrated a significant elevation of serum granulocyte/ macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 levels in the aged op/op mice. To examine whether GM-CSF and/or IL-3 could correct osteopetrosis in young op/op mice, 5 ng of recombinant murine (rm)GM-CSF and/or 100 ng of rmIL-3 were injected daily into young op/op mice. In these treated young op/op mice, the bone marrow cavities were expanded significantly at 2 weeks after administration, associated with significantly increased numbers of TRAP-positive cells and bone marrow macrophages. TRAP-positive cells increased in number with days after injection. These results suggest that GM-CSF and IL-3 induce the development of osteoclasts to correct osteopetrosis in the op/op mice with aging.

• Authors: Y Y Myint, K Miyakawa, M Naito, L D Shultz, Y Oike, K Yamamura, K Takahashi
• Journal: The American journal of pathology (Am J Pathol) Vol. 154 Issue 2 Pg. 553-66 (Feb 1999) ISSN: 0002-9440 [Print] United States
• PMID: 10027413 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Drug Combinations
• Interleukin-3
• Recombinant Proteins
• RNA
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Aging
• Animals
• Bone Marrow (drug effects, pathology)
• Cell Count (drug effects)
• Drug Combinations
• Enzyme-Linked Immunosorbent Assay
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (blood, pharmacology, therapeutic use)
• Hindlimb (diagnostic imaging, drug effects, pathology)
• Interleukin-3 (blood, pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Mutant Strains (blood)
• Mutation
• Osteoclasts (drug effects)
• Osteopetrosis (blood, drug therapy, genetics)
• RNA (analysis)
• Radiography
• Recombinant Proteins (pharmacology, therapeutic use)
• Reverse Transcriptase Polymerase Chain Reaction