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Bone particles from osteopetrotic mice not cured by bone marrow transplants are resorbed in normal littermates
Abstract:
Osteosclerotic (oc/oc) and osteopetrotic (op/op) mice are not cured by bone marrow transplantation from normal littermates. The possibility that this is due to production of poorly resorbable bone was examined by comparing the fate of mutant and normal bone particles implanted subcutaneously in normal hosts. Bone, removed aseptically from calvarial and tibial sites of normal littermates and mutants, was cleaned of adherent soft tissue, ground and sieved to a particle size of 70-300 micron. Aliquots (17-20 mg) of bone from each phenotype of each stock were pelleted and implanted beneath the anterior thoracic skin of normal littermates for two weeks. Particle density in tissue sections was determined as percent of field by a point-counting method. Giant cell response was recorded as number per high-power field. Percent bone present initially was determined in pellets implanted for less than 24 hr. Bone particles were reduced in each pellet with time, about 25% of the original volume being removed in two weeks. No statistically significant differences were noted in the rates of disappearance of mutant and normal bone or in the percentage or number of giant cells in implants of mutant and normal bone in either stock. Furthermore, these values were not different from identical studies in microphthalmic mice, an osteopetrotic stock cured by bone marrow transplantation. These data suggest that the failure of osteopetrotic and osteosclerotic mice to be cured by bone marrow transplants from normal littermates is not due to the presence of unresorbable bone.
Insights
Osteosclerotic (oc/oc) and osteopetrotic (op/op) mice bone marrow transplantation fails because their bone is not resorbable. This study found mutant and normal bone particles disappeared at similar rates, suggesting bone resorption is not the cause.
Area of Science:
- Skeletal Biology
- Transplantation Immunology
- Genetics
Background:
- Osteosclerotic (oc/oc) and osteopetrotic (op/op) mouse models exhibit impaired bone resorption.
- These mouse models are not cured by bone marrow transplantation (BMT) from normal littermates.
- The cause of BMT failure in these models remains unclear, with poorly resorbable bone being a potential factor.
Purpose of the Study:
- To investigate whether the production of poorly resorbable bone contributes to the failure of BMT in osteosclerotic and osteopetrotic mice.
- To compare the resorption rates of mutant and normal bone particles in vivo.
Main Methods:
- Bone particles from normal, osteosclerotic (oc/oc), and osteopetrotic (op/op) mice were implanted subcutaneously into normal host mice.
- Bone particle fate was assessed over two weeks by measuring particle density and giant cell response.
- Resorption rates were compared between mutant and normal bone, and with a responsive osteopetrotic model (microphthalmic mice).
Main Results:
- Both mutant and normal bone particles showed similar rates of disappearance over two weeks, with approximately 25% of the original volume being removed.
- No significant differences were observed in the giant cell response between implants of mutant and normal bone.
- These findings were consistent across different osteopetrotic models, including one responsive to BMT.
Conclusions:
- The failure of bone marrow transplantation to cure osteosclerotic (oc/oc) and osteopetrotic (op/op) mice is not due to the production of unresorbable bone.
- Bone resorption capacity in these mutant mice appears adequate for clearing implanted bone particles.
- Alternative explanations for BMT failure in these skeletal disease models should be explored.