Naslov
Osteoblastic activity in the OIM mouse

Autori
Kalajzic, Ivo ; Terzic, Janos ; Mack, Kris ; Visnjic, Dora ; Naprta, Anica ; Gronowicz, Gloria ; Clark, Stephen ; Rowe, David

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Bone 23:5 (Suppl), S461, 1134, 1998 / - , 1998

Skup
Second Joint Meeting of ASBMR and IBMS

Mjesto i datum
San Francisco (CA), Sjedinjene Američke Države, 01.12.1998. - 06.12.1998

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
OIM; osteoblast

Sažetak
We bred the Col1A1 promoter/ CAT reporter (ColCAT 3.6) transgene into OIM mouse line to provide a sensitive marker for bone formation in this model of osteogenesis imperfecta (OI). Humeri adn calvariae of 7 days, 1 and 3 months of age were analyzed for CAT enzymatic activity. There was no difference between the genotypes (oim/oim, oim/+, +/+) at age of 7 days and 1 month. At three months when the phase of rapid growth is over there was a major drop in CAT activity in all three genotypes, but the fall was much smaller in oim/oim mice (50%) than in other two groups (80%). In additional experiments of 3 month old mice, both CAT activity and mRNA levels of oim/oim was 4 fold and oim/+ was 2 fold greater than +/+ mice. In the same mice, mRNA for Col1A1, BSP and OCwere two fold higher in the oim/oim mice while the oim/+ was indistinguishable from +/+. CAT immunofluorescence of humeri can be detected in both periosteal and endosteal surfaces of all threee genotypes. However the oim/oim mive have highly posiotive regions including cortical osteocytes and both periosteal and endosteal surfaces. By 5 months of age, CAT mRNA and activity is still 2 fold greater in oim/oim while mRNA for the bone associated mRNAs was increased 1.5 fold. No increase in CAT or bone associated mRNA was present in the OIM/+mice. of interest are the marrow stromal fibroblasts derived from the mice. At 3 mo., equal number of mAP+ colonies were obtained from each genotype, but at 5 mo. colonies were slower to develop in oim/oim and oim/+. Thus the oim mutattion induces a persisitently stimulated osteoblast that may lead to stem cell exhaustion with advancing age. Static histomorphometry of oim/oim showed significantly smaller cortical width and exceptional osteoclastic activity that was more pronounced in the periosteal layer. Urinary excretion of DPD was increased less than 2 fold in oim/oim while the excretion was not significantly increased in oim/+ mice. Calcein double labeling yieldied a clear double fluorescent band in the +/* mice but only a single broad label in oim/oim mice. We conclude that OI bone is undergoing extremely high turnover which is not detrected by the diagnostic methods used in other osteopenic deiseases. use of transgene markers that reflect synthetic activity of resident osteoblast and activated preosteoblasts may be the most sensitive marker of an intervention designed to increase bone strength in OI.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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