Because JunB is an essential gene for placentation, it was conditionally deleted in the embryo proper. JunBDelta/Delta mice are born viable, but develop severe low turnover osteopenia caused by apparent cell-autonomous osteoblast and osteoclast defects before a chronic myeloid leukemia-like disease. Although JunB was reported to be a negative regulator of cell proliferation, junBDelta/Delta osteoclast precursors and osteoblasts show reduced proliferation along with a differentiation defect in vivo and in vitro. Mutant osteoblasts express elevated p16(INK4a) levels, but exhibit decreased cyclin D1 and cyclin A expression. Runx2 is transiently increased during osteoblast differentiation in vitro, whereas mature osteoblast markers such as osteocalcin and bone sialoprotein are strongly reduced. To support a cell-autonomous function of JunB in osteoclasts, junB was inactivated specifically in the macrophage-osteoclast lineage. Mutant mice develop an osteopetrosis-like phenotype with increased bone mass and reduced numbers of osteoclasts. Thus, these data reveal a novel function of JunB as a positive regulator controlling primarily osteoblast as well as osteoclast activity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171977 | PMC |
| http://dx.doi.org/10.1083/jcb.200308155 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
DAMPs, PAMPs, NLRs, RIGs, CLRs and TLRs - Understanding the Alphabet Soup in the Context of Bone Biology.
Curr Osteoporos Rep
January 2025
Department of Immunology, Tufts University, Boston, MA, 02111, USA.
Purpose Of Review: The purpose of this review is to summarize the current understanding of cell-autonomous innate immune pathways that contribute to bone homeostasis and disease.
Recent Findings: Germ-line encoded pattern recognition receptors (PRRs) are the first line of defense against danger and infections. In the bone microenvironment, PRRs and downstream signaling pathways, that mount immune defense, interface intimately with the core cellular processes in bone cells to alter bone formation and resorption.
In nondiabetic C57BL/6J mice, canagliflozin affects the skeleton in a sex- and age-dependent manner.
JBMR Plus
December 2024
Center for Molecular Medicine, MaineHealth Institute for Research, Scarborough, ME 04074, United States.
Canagliflozin (CANA) is a sodium glucose cotransporter-2 inhibitor that reduces blood glucose levels. Sodium glucose cotransporter-2 is primarily expressed in the kidney, but not in any bone cells, therefore effects on the skeleton are likely to be non-cell autonomous. Originally developed to treat type II diabetes, CANA use has expanded to treat cardiovascular and renovascular disease.
View Article and Find Full Text PDFGlycogen Storage Disease Type I and Bone: Clinical and Cellular Characterization.
Calcif Tissue Int
November 2024
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.
View Article and Find Full Text PDFOsteopetrosis-like disorders induced by osteoblast-specific retinoic acid signaling inhibition in mice.
Bone Res
October 2024
Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Osteopetrosis is an inherited metabolic disease, characterized by increased bone density and narrow marrow cavity. Patients with severe osteopetrosis exhibit abnormal bone brittleness, anemia, and infection complications, which commonly cause death within the first decade of life. Pathologically, osteopetrosis impairs not only the skeletal system, but also the hemopoietic and immune systems during development, while the underlying osteoimmunological mechanisms remain unclear.
View Article and Find Full Text PDFInactivation of spermine synthase in mice causes osteopenia due to reduced osteoblast activity.
J Bone Miner Res
October 2024
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Hamburg, Germany.
Spermine synthase, encoded by the SMS gene, is involved in polyamine metabolism, as it is required for the synthesis of spermine from its precursor molecule spermidine. Pathogenic variants of SMS are known to cause Snyder-Robinson syndrome (SRS), an X-linked recessive disorder causing various symptoms, including intellectual disability, muscular hypotonia, infertility, but also skeletal abnormalities, such as facial dysmorphisms and osteoporosis. Since the impact of a murine SMS deficiency has so far only been analyzed in Gy mice, where a large genomic deletion also includes the neighboring Phex gene, there is only limited knowledge about the potential role of SMS in bone cell regulation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!