ArticleMolecular and cellular biology2016
Smpd3 Expression in both Chondrocytes and Osteoblasts Is Required for Normal Endochondral Bone Development.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
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- TNAP and PHOSPHO1 function synergistically to afford critical control over the mineralisation of the postnatal murine skeleton.bioRxiv : the preprint server for biology · 2026Article
- Blood transcriptomic associations of epigenetic age in adolescents.Epigenetics · 2025Article
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Electroacupuncture Ameliorates Knee Osteoarthritis By Rebalancing T Cell Homeostasis as Revealed By Immune Repertoire (IR) Sequencing.Combinatorial chemistry & high throughput screening · 2025Article
- Challenging the conventional wisdom: Re-evaluating Smpd3's role in extracellular vesicle biogenesis.Journal of extracellular biology · 2024Article
- Article
- SMPD3 expression is spatially regulated in the developing embryo by SOXE factors.Developmental biology · 2024Article
- Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery.Cell biochemistry and function · 2023Article
- Article
- Review
- Binge Ethanol Exposure in Mice Represses Expression of Genes Involved in Osteoblast Function and Induces Expression of Genes Involved in Osteoclast Differentiation Independently of Endogenous Catalase.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Neonatal stroke enhances interaction of microglia-derived extracellular vesicles with microglial cells.Neurobiology of disease · 2021Article
- Effects of an Environmentally Relevant Mixture of Organophosphate Esters Derived From House Dust on Endochondral Ossification in Murine Limb Bud Cultures.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Ablation ofJBMR plus · 2021Article
- Long-term use of fluoxetine accelerates bone loss through the disruption of sphingolipids metabolism in bone marrow adipose tissue.Translational psychiatry · 2020Article
- How To Build a Bone: PHOSPHO1, Biomineralization, and Beyond.JBMR plus · 2019Review
- Role of SMPD3 during Bone Fracture Healing and Regulation of Its Expression.Molecular and cellular biology · 2019Article
- Mechanism of Bone Mineralization.Cold Spring Harbor perspectives in medicine · 2018Review
- SMPD3 deficiency perturbs neuronal proteostasis and causes progressive cognitive impairment.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Sphingomyelin phosphodiesterase 3 (SMPD3), a lipid-metabolizing enzyme present in bone and cartilage, has been identified to be a key regulator of skeletal development. A homozygous loss-of-function mutation called fragilitas ossium (fro) in the Smpd3 gene causes poor bone and cartilage mineralization resulting in severe congenital skeletal deformities. Here we show that Smpd3 expression in ATDC5 chondrogenic cells is downregulated by parathyroid hormone-related peptide through transcription factor SOX9. Furthermore, we show that transgenic expression of Smpd3 in the chondrocytes of fro/fro mice corrects the cartilage but not the bone abnormalities. Additionally, we report the generation of Smpd3(flox/flox) mice for the tissue-specific inactivation of Smpd3 using the Cre-loxP system. We found that the skeletal phenotype in Smpd3(flox/flox); Osx-Cre mice, in which the Smpd3 gene is ablated in both late-stage chondrocytes and osteoblasts, closely mimics the skeletal phenotype in fro/fro mice. On the other hand, Smpd3(flox/flox); Col2a1-Cre mice, in which the Smpd3 gene is knocked out in chondrocytes only, recapitulate the fro/fro mouse cartilage phenotype. This work demonstrates that Smpd3 expression in both chondrocytes and osteoblasts is required for normal endochondral bone development.
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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.