ArticleThe Journal of biological chemistry2014
Lysophosphatidic acid receptor type 1 (LPA1) plays a functional role in osteoclast differentiation and bone resorption activity.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Metabolomic biomarkers of low BMD: a systematic review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- EBV promotes alveolar trabecula resorption via extracellular vesicle remodeling by group IIA secreted phospholipase AJournal of lipid research · 2026Article
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Lipid metabolism in age-related musculoskeletal disorders: insights into sarcopenia and osteoporosis.BMC biology · 2025Review
- miR-383-3p and miR-6951-3p activate cell proliferation through the regulation of genes related to hypertelorism.Frontiers in cell and developmental biology · 2025Article
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Autotaxin/Lysophosphatidic Acid Axis: From Bone Biology to Bone Disorders.International journal of molecular sciences · 2022Review
- Lysophosphatidic acid receptors 2 and 3 regulate erythropoiesis at different hematopoietic stages.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Article
- Rheumatoid Arthritis in the View of Osteoimmunology.Biomolecules · 2020Review
- [Research progress on the biological regulatory function of lysophosphatidic acid in bone tissue cells].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2020Review
- The roles of autotaxin/lysophosphatidic acid in immune regulation and asthma.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- A Membranome-Centered Approach Defines Novel Biomarkers for Cellular Subtypes in the Intervertebral Disc.Cartilage · 2020Article
- Lysophosphatidic Acid and Hematopoiesis: From Microenvironmental Effects to Intracellular Signaling.International journal of molecular sciences · 2020Review
- Review
- Osteoclast-Derived Autotaxin, a Distinguishing Factor for Inflammatory Bone Loss.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
- microRNA-329 reduces bone cancer pain through the LPAR1-dependent LPAR1/ERK signal transduction pathway in mice.Therapeutic advances in medical oncology · 2019Article
- The role of GPCRs in bone diseases and dysfunctions.Bone research · 2019Review
- Role of CX3CL1/CX3CR1 Signaling Axis Activity in Osteoporosis.Mediators of inflammation · 2019Review
- Regulation of tumor cell - Microenvironment interaction by the autotaxin-lysophosphatidic acid receptor axis.Advances in biological regulation · 2019Review
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysophosphatidic acid (LPA) is a natural bioactive lipid that acts through six different G protein-coupled receptors (LPA1-6) with pleiotropic activities on multiple cell types. We have previously demonstrated that LPA is necessary for successful in vitro osteoclastogenesis of bone marrow cells. Bone cells controlling bone remodeling (i.e. osteoblasts, osteoclasts, and osteocytes) express LPA1, but delineating the role of this receptor in bone remodeling is still pending. Despite Lpar1(-/-) mice displaying a low bone mass phenotype, we demonstrated that bone marrow cell-induced osteoclastogenesis was reduced in Lpar1(-/-) mice but not in Lpar2(-/-) and Lpar3(-/-) animals. Expression of LPA1 was up-regulated during osteoclastogenesis, and LPA1 antagonists (Ki16425, Debio0719, and VPC12249) inhibited osteoclast differentiation. Blocking LPA1 activity with Ki16425 inhibited expression of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) and dendritic cell-specific transmembrane protein and interfered with the fusion but not the proliferation of osteoclast precursors. Similar to wild type osteoclasts treated with Ki16425, mature Lpar1(-/-) osteoclasts had reduced podosome belt and sealing zone resulting in reduced mineralized matrix resorption. Additionally, LPA1 expression markedly increased in the bone of ovariectomized mice, which was blocked by bisphosphonate treatment. Conversely, systemic treatment with Debio0719 prevented ovariectomy-induced cancellous bone loss. Moreover, intravital multiphoton microscopy revealed that Debio0719 reduced the retention of CX3CR1-EGFP(+) osteoclast precursors in bone by increasing their mobility in the bone marrow cavity. Overall, our results demonstrate that LPA1 is essential for in vitro and in vivo osteoclast activities. Therefore, LPA1 emerges as a new target for the treatment of diseases associated with excess bone loss.
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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.