ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2008
Cellular mechanism of decreased bone in Brtl mouse model of OI: imbalance of decreased osteoblast function and increased osteoclasts and their precursors.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- An update on the role of RANKL-RANK/osteoprotegerin and WNT-ß-catenin signaling pathways in pediatric diseases.World journal of pediatrics : WJP · 2019Pooled it
- Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders.BioMed research international · 2014Pooled it
- Molecular drivers of osteogenesis imperfecta: a cellular and extracellular collagen disease.Clinical science (London, England : 1979) · 2025Review
- LC3 and GABARAP independent autophagy of misfolded procollagen in mouse osteoblasts.Autophagy · 2025Article
- Combined antiresorptive and new anabolic drug approach in osteogenesis imperfecta zebrafish models.JBMR plus · 2025Article
- Review
- Complex Analysis of Micronutrient Levels and Bone Mineral Density in Patients with Different Types of Osteogenesis Imperfecta.Diagnostics (Basel, Switzerland) · 2025Article
- Characterization of a Novel Col1a1Calcified tissue international · 2025Article
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Bone Quality and Mineralization and Effects of Treatment in Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Article
- HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation.JCI insight · 2024Article
- Brain-Type Creatine Kinase Release from Cultured Osteoclasts Exposed to Neridronate in Children Affected by Osteogenesis Imperfecta Type 1.Biomedicines · 2023Article
- Zebrafish Tric-b is required for skeletal development and bone cells differentiation.Frontiers in endocrinology · 2023Article
- Murine Animal Models in Osteogenesis Imperfecta: The Quest for Improving the Quality of Life.International journal of molecular sciences · 2022Review
- ER, Mitochondria, and ISR Regulation by mt-HSP70 and ATF5 upon Procollagen Misfolding in Osteoblasts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Article
- Dissecting the phenotypic variability of osteogenesis imperfecta.Disease models & mechanisms · 2022Article
- 4PBA reduces growth deficiency in osteogenesis imperfecta by enhancing transition of hypertrophic chondrocytes to osteoblasts.JCI insight · 2022Article
- Osteogenesis Imperfecta: Mechanisms and Signaling Pathways Connecting Classical and Rare OI Types.Endocrine reviews · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The Brtl mouse, a knock-in model for moderately severe osteogenesis imperfecta (OI), has a G349C substitution in half of type I collagen alpha1(I) chains. We studied the cellular contribution to Brtl bone properties. Brtl cortical and trabecular bone are reduced before and after puberty, with BV/TV decreased 40-45%. Brtl ObS/BS is comparable to wildtype, and Brtl and wildtype marrow generate equivalent number of colony-forming units (CFUs) at both ages. However, OcS/BS is increased in Brtl at both ages (36-45%), as are TRACP(+) cell numbers (57-47%). After puberty, Brtl ObS/BS decreases comparably to wildtype mice, but osteoblast matrix production (MAR) decreases to one half of wildtype values. In contrast, Brtl OcS falls only moderately (approximately 16%), and Brtl TRACP staining remains significantly elevated compared with wildtype. Consequently, Brtl BFR decreases from normal at 2 mo to one half of wildtype values at 6 mo. Immunohistochemistry and real-time RT-PCR show increased RANK, RANKL, and osteoprotegerin (OPG) levels in Brtl, although a normal RANKL/OPG ratio is maintained. TRACP(+) precursors are markedly elevated in Brtl marrow cultures and form more osteoclasts, suggesting that osteoclast increases arise from more RANK-expressing precursors. We conclude that osteoblasts and osteoclasts are unsynchronized in Brtl bone. This cellular imbalance results in declining BFR as Brtl ages, consistent with reduced femoral geometry. The disparity in cellular number and function results from poorly functioning osteoblasts in addition to increased RANK-expressing precursors that respond to normal RANKL/OPG ratios to generate more bone-resorbing osteoclasts. Interruption of the stimulus that increases osteoclast precursors may lead to novel OI therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.