skeleton
• in response to 500 ng/mL rhBMP-2, cultured mesenchymal cells prepared from the thigh muscle of E14.5-E15.5 mutant embryos display enhanced osteoblastic differentiation, with ~92% of mutant embryonic cells differentiated into alkaline phosphatase (ALP)-positive cells relative to only ~33% of wild-type cells
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• at 3 weeks after rib fracture, homozygotes show a significant increase in the rate of bone healing relative to wild-type mice (50.6% in 9/16 ribs vs. 25% in 4/16 ribs, respectively), along with a faster and longer expression of PCNA and BMP-4 mRNAs
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• at 12 weeks of age, mutant long bones exhibit an increased width, with no change in bone length relative to wild-type littermates
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• at 12 weeks of age, mutant femurs display an increased diameter, as shown by X-ray analysis
• the bone marrow space is proportionally enlarged, as observed in ectopic bones induced by rhBMP-2
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• at 5 weeks of age, the number of activated periosteal osteoblasts is increased in mutant femurs relative to wild-type femurs
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• at E13.0 and E13.5, homozygotes exhibit an earlier onset of cartilage formation relative to wild-type mice
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ectopic bone
(
J:77112
)
• at 3 weeks after implantation of bone-inducing BMP/atelocollagen pellets, homozygotes exhibit increased ectopic bone formation in muscle tissues, with rhBMP-2induced ectopic ossicles being significantly greater in size and in calcium content than those induced in wild-type mice
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• at E14.5, homozygotes exhibit an earlier onset of ossification in the calvaria and tibia relative to wild-type mice
• however, the long bones of mutant and wild-type mice appear to be similar in length at E14.5
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homeostasis/metabolism
• at 8 weeks of age, homozygotes display a significant increase in serum ALP activity relative to wild-type littermates (406 17 IU/L vs. 277 9 IU/L, respectively)
• however, serum calcium and inorganic phosphate concentrations remain within normal range
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• at 3 weeks after rib fracture, homozygotes show a significant increase in the rate of bone healing relative to wild-type mice (50.6% in 9/16 ribs vs. 25% in 4/16 ribs, respectively), along with a faster and longer expression of PCNA and BMP-4 mRNAs
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limbs/digits/tail
• at 12 weeks of age, mutant femurs display an increased diameter, as shown by X-ray analysis
• the bone marrow space is proportionally enlarged, as observed in ectopic bones induced by rhBMP-2
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cellular
• in response to 500 ng/mL rhBMP-2, cultured mesenchymal cells prepared from the thigh muscle of E14.5-E15.5 mutant embryos display enhanced osteoblastic differentiation, with ~92% of mutant embryonic cells differentiated into alkaline phosphatase (ALP)-positive cells relative to only ~33% of wild-type cells
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