skeleton
• the number of ostoblast colony forming units cultured from bone marrow of 2-month old mice is half that of controls
• in vitro bone nodule formation is reduced by more than half in these bone marrow cultures
• committed osteoblast progenitors have a 7% increase in doubling time compared to controls
• the number of osteoblast progenitors isolated from bone marrow cultures is reduced
• however, the ratio of osteoblast progenitors to total number of stromal progenitors is the same
|
• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells
• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis
|
• bone formation is essentially normal at 2 months of age but is dramatically reduced by 6 months of age
|
• the absolute number of osteoclasts is reduced by more than 40% in both 2- and 9- month old femurs
• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells
|
• bone mineral content does not change between 2 months of age to 12 months of age while mineral content is increased in wild-type mice during this time period
|
• femurs have 27% fewer trabeculae compared with control bones at 4 months of age and 58% compared with bones at 15 months of age
|
osteoporosis
(
J:83409
)
• mice one year of age have the same bone mass density as 8 week old mice, which is significantly less than the bone mass of one year old wild-type mice
• the greatest decrease in bone mass density occurs in vertebrae
|
• the percent of osteoid in femurs are significantly lower in both 4- and 15- month old bones
|
• bone formation is essentially normal at 2 months of age but is dramatically reduced by 6 months of age
|
• compression testing of 15-month old vertebrae shows the bone is not as stiff and is substantially weaker and more compliant than bones from wild-type animals
• the yield stress and failure stress of vertebrae are reduced by about a third while the elastic modulus is half that of controls
• femurs from 15-month-old mice have a similar stiffness to wild-type bones but are weaker and considerably more brittle
|
hematopoietic system
• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells
• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis
|
• the total number of stromal progenitors found in bone marrow is reduced in 2- and 7- month old mice by 45% and 67%, respectively, compared to controls
• serial passaging of bone marrow stromal cultures reduces the number of stromal progenitors by more than half per passage, indicating a defect in self renewal
|
• the absolute number of osteoclasts is reduced by more than 40% in both 2- and 9- month old femurs
• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells
|
adipose tissue
• bone marrow stroma contains two-thirds less adipocyte progenitors than controls
|
immune system
• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells
• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis
|
• the absolute number of osteoclasts is reduced by more than 40% in both 2- and 9- month old femurs
• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells
|
cellular
• the number of ostoblast colony forming units cultured from bone marrow of 2-month old mice is half that of controls
• in vitro bone nodule formation is reduced by more than half in these bone marrow cultures
• committed osteoblast progenitors have a 7% increase in doubling time compared to controls
• the number of osteoblast progenitors isolated from bone marrow cultures is reduced
• however, the ratio of osteoblast progenitors to total number of stromal progenitors is the same
|
• osteoblast and splenic co-cultures generated less than 10% of the osteoclasts found in co-cultures of wild-type cells
• when mutant osteoblastic cells were used with wild-type splenocytes, markedly reduced numbers of wild-type osteoclasts are generated indicating a primary stromal cell defect in osteoclastogenesis
|
• bone formation is essentially normal at 2 months of age but is dramatically reduced by 6 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
osteoporosis | DOID:11476 |
OMIM:166710 |
J:83409 |