ArticleCommunications biology2019
Murine osteoclasts secrete serine protease HtrA1 capable of degrading osteoprotegerin in the bone microenvironment.
Article in Communications biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Exploring causal associations between the plasma proteome and bone mineral density: a Mendelian randomization study.Endocrine connections · 2026Article
- The molecular and functional interplay between the osteopetrosis-associated proteins SNX10, OSTM1, and CLC-7 during mouse osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis.Cell death & disease · 2026Article
- Astragalin Attenuates Bone Destruction and the Progression of Bone Metastasis in Breast Cancer.Cancers · 2025Article
- Cystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region.Nature communications · 2024Article
- HTRA1 from OVX rat osteoclasts causes detrimental effects on endplate chondrocytes through NF-κB.Heliyon · 2023Article
- Transcriptomic Differences Underlying the Activin-A Induced Large Osteoclast Formation in Both Healthy Control and Fibrodysplasia Ossificans Progressiva Osteoclasts.International journal of molecular sciences · 2023Article
- Cathepsin K degrades osteoprotegerin to promote osteoclastogenesis in vitro.In vitro cellular & developmental biology. Animal · 2023Article
- RANKL biology.Bone · 2022Review
- Osteoimmunology in Periodontitis: Local Proteins and Compounds to Alleviate Periodontitis.International journal of molecular sciences · 2022Review
- Construction and evaluation of detachable bone-targeting MOF carriers for the delivery of proteasome inhibitors.RSC advances · 2022Article
- Microcracks on the Rat Root Surface Induced by Orthodontic Force, Crack Extension Simulation, and Proteomics Study.Annals of biomedical engineering · 2021Article
- RANKL and osteoimmunology in periodontitis.Journal of bone and mineral metabolism · 2021Review
- Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques.Frontiers in endocrinology · 2021Review
- Molecular structure and the role of high-temperature requirement protein 1 in skeletal disorders and cancers.Cell proliferation · 2020Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoclasts are multinucleated cells responsible for bone resorption. The differentiation of osteoclasts from bone marrow macrophages (BMMs) is induced by receptor activator of NF-κB ligand (RANKL). Osteoprotegerin (OPG), a decoy receptor of RANKL, inhibits osteoclastogenesis by blocking RANKL signaling. Here we investigated the degradation of OPG in vitro. Osteoclasts, but not BMMs, secreted OPG-degrading enzymes. Using mass spectrometry and RNA-sequencing analysis, we identified high-temperature requirement A serine peptidase 1 (HtrA1) as an OPG-degrading enzyme. HtrA1 did not degrade OPG pre-reduced by dithiothreitol, suggesting that HtrA1 recognizes the three-dimensional structure of OPG. HtrA1 initially cleaved the amide bond between leucine 90 and glutamine 91 of OPG, then degraded OPG into small fragments. Inhibitory activity of OPG on RANKL-induced osteoclastogenesis was suppressed by adding HtrA1 in RAW 264.7 cell cultures. These results suggest that osteoclasts potentially prepare a microenvironment suitable for osteoclastogenesis. HtrA1 may be a novel drug target for osteoporosis.
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