ArticleDisease models & mechanisms2016
Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 98 citations in OpenAlex.
- Molecular mechanisms, therapeutic strategies, and inter-organ fibrosis crosstalk of Gla proteins in cardiovascular disease.Communications biology · 2026Review
- Mechanosensitive Piezo1/Osteocalcin/Irisin Axis Protects Against Disuse-Induced Muscle Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice.Bone research · 2026Article
- Decoding the secretory blueprint of bone healing: from gradients to regeneration.Frontiers in cell and developmental biology · 2026Review
- LP533401 treatment alters vitamin K metabolism, bone Gla-OC/Glu-OC ratios, and improves mineral status of the skeleton in rats with chronic kidney disease.Frontiers in pharmacology · 2026Article
- Molecular signaling pathways in osteoarthritis and biomaterials for cartilage regeneration: a review.Bioengineered · 2025Review
- Osteocalcin deficiency attenuates neointima formation after vascular injury in rat.BMC cardiovascular disorders · 2025Article
- Rat models of musculoskeletal lysosomal storage disorders and their role in pre-clinical evaluation of gene therapy approaches.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Bone and muscle crosstalk in ageing and disease.Nature reviews. Endocrinology · 2025Review
- Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs.Bone research · 2025Review
- Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.International journal of biological sciences · 2025Article
- The Role of Bone-Derived Osteocalcin in Testicular Steroidogenesis: Contributing Factor to Male Fertility.Diseases (Basel, Switzerland) · 2024Review
- Wnt7b overexpression in osteoblasts stimulates bone formation and reduces obesity in mice on a high-fat diet.JBMR plus · 2024Article
- Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.International journal of molecular sciences · 2024Review
- Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.Reviews in endocrine & metabolic disorders · 2024Review
- Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Plasma undercarboxylated osteocalcin dynamics with glycemic stress reflects insulin sensitivity and beta-cell function in humans with and without T2DM.Metabolism open · 2023Article
- Review
- The Past, Present, and Future of Genetically Engineered Mouse Models for Skeletal Biology.Biomolecules · 2023Review
- Abaloparatide Maintains Normal Rat Blood Calcium Level in Part Via 1,25-Dihydroxyvitamin D/osteocalcin Signaling Pathway.Endocrinology · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap) gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA), glucose tolerance testing (GTT), insulin tolerance testing (ITT), microcomputed tomography (µCT), and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research.
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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.