ArticlePloS one2011
Control of bone resorption by semaphorin 4D is dependent on ovarian function.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Insights into the mechanism of vascular endothelial cells on bone biology.Bioscience reports · 2021Pooled it
- Brain-Bone Axis in Physiological and Pathological Conditions.International journal of molecular sciences · 2025Review
- Skeletal interoception and prospective application in biomaterials for bone regeneration.Bone research · 2025Review
- Impact of Different Cell Types on the Osteogenic Differentiation Process of Mesenchymal Stem Cells.Stem cells international · 2025Review
- Single nucleus/cell RNA-seq of the chicken hypothalamic-pituitary-ovarian axis offers new insights into the molecular regulatory mechanisms of ovarian development.Zoological research · 2024Article
- Bone-organ axes: bidirectional crosstalk.Military Medical Research · 2024Review
- Review
- Diverse roles for axon guidance pathways in adult tissue architecture and function.Natural sciences (Weinheim, Germany) · 2022Article
- Locally Secreted Semaphorin 4D Is Engaged in Both Pathogenic Bone Resorption and Retarded Bone Regeneration in a Ligature-Induced Mouse Model of Periodontitis.International journal of molecular sciences · 2022Article
- Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis.International journal of molecular sciences · 2022Article
- Spatial Organization of Osteoclastic Coupling Factors and Their Receptors at Human Bone Remodeling Sites.Frontiers in molecular biosciences · 2022Article
- Tenofovir Modulates Semaphorin 4D Signaling and Regulates Bone Homeostasis, Which Can Be Counteracted by Dipyridamole and Adenosine A2A Receptor.International journal of molecular sciences · 2021Article
- Crosstalk between Bone and Nerves within Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Review
- Bone Cell Communication Factors Provide a New Therapeutic Strategy for Osteoporosis.Chonnam medical journal · 2020Review
- Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients.Journal of bone oncology · 2019Article
- Coupling factors involved in preserving bone balance.Cellular and molecular life sciences : CMLS · 2019Review
- Multiple Myeloma and Bone: The Fatal Interaction.Cold Spring Harbor perspectives in medicine · 2018Review
- Adenosine AFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Low expression of SEMA6C accelerates the primordial follicle activation in the neonatal mouse ovary.Journal of cellular and molecular medicine · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D -/- mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D -/- mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function.
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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.