Lack of bone resorption in osteosclerotic (oc/oc) mice is due to a defect in osteoclast progenitors rather than the local microenvironment provided by osteoblastic cells.
In a co-culture system of mouse spleen cells and osteoblastic cells, we have demonstrated that a suitable microenvironment must be provided by osteoblastic cells in order for osteoclast-like multinucleated cell (MNC) formation. Using this co-culture system, we examined the pathogenetic mechanism underlying the lack of bone resorption in osteosclerotic oc/oc mice. Numerous tartrate-resistant acid phosphatase (TRAP, an osteoclast marker enzyme)-positive MNCs were formed in response to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] both in co-cultures of oc/oc spleen cells and normal osteoblastic cells and in those of normal spleen cells and oc/oc osteoblastic cells. TRAP-positive MNCs derived from normal spleen cells tended to spread out on culture dishes, whereas those from oc/oc spleen cells remained as small, compact MNCs. When TRAP-positive MNCs enriched from co-cultures of normal spleen cells and oc/oc osteoblastic cells were cultured on dentine slices, they formed numerous resorption pits with ruffled borders and clear zones. In contrast, none of the TRAP-positive MNCs derived from oc/oc spleen cells formed either ruffled borders or resorption pits. These results indicate that the lack of bone resorption in oc/oc mice is due to a defect in osteoclast progenitors rather than the local microenvironment provided by osteoblastic cells.
Udagawa
N
N
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Sasaki
T
T
Akatsu
T
T
Takahashi
N
N
Tanaka
S
S
Tamura
T
T
Tanaka
H
H
Suda
T
T
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology*; D002116:Calcitonin / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002450:Cell Communication; D002478:Cells, Cultured; D051379:Mice; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D010026:Osteosclerosis / Q000473:pathology / Q000503:physiopathology*; D013154:Spleen / Q000166:cytology / Q000502:physiology
D015415:Biomarkers; D002116:Calcitonin; D000135:Acid Phosphatase; D002117:Calcitriol