Osteoblastic response to the defective matrix in the osteogenesis imperfecta murine (oim) mouse.
This work examines the cellular pathophysiology associated with the weakened bone matrix found in a murine model of osteogenesis imperfecta murine (oim). Histomorphometric analysis of oim/oim bone showed significantly diminished bone mass, and the osteoblast and osteoclast histomorphometric parameters were increased in the oim/oim mice, compared with wild-type (+/+) mice. To assess osteoblast activity, a rat Col1a1 promoter linked to the chloramphenicol acetyltransferase reporter transgene was bred into the oim model. At 8 d and 1 month of age, no difference in transgene activity between oim and control mice was observed. However, at 3 months of age, chloramphenicol acetyl transferase activity was elevated in oim/oim;Tg/Tg, compared with +/+;Tg/Tg and oim/+;Tg/Tg. High levels of urinary pyridinoline crosslinks in the oim/oim;Tg/Tg mice were present at all ages, reflecting continuing high bone resorption. Our data portray a state of ineffective osteogenesis in which the mutant mouse never accumulates a normal quantity of bone matrix. However, it is only after the completion of the rapid growth phase that the high activity of the oim/oim osteoblast can compensate for the high rate of bone resorption. This relationship between bone formation and resorption may explain why the severity of osteogenesis imperfecta decreases after puberty is completed. The ability to quantify high bone turnover and advantages of using a transgene that reflects osteoblast lineage activity make this a useful model for studying interventions designed to improve the bone strength in osteogenesis imperfecta.
Kalajzic
I
I
Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
Terzic
J
J
Rumboldt
Z
Z
Mack
K
K
Naprta
A
A
Ledgard
F
F
Gronowicz
G
G
Clark
S H
SH
Rowe
D W
DW
D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D001846:Bone Development / Q000502:physiology; D001857:Bone Matrix / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000502:physiology*; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013977:Tibia / Q000166:cytology
D000596:Amino Acids; D015415:Biomarkers; D024042:Collagen Type I; D012333:RNA, Messenger; C036020:deoxypyridinoline; D015500:Chloramphenicol O-Acetyltransferase