ArticleCell death and differentiation2021
Site-1 protease controls osteoclastogenesis by mediating LC3 transcription.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- CDC25C downregulation suppresses HCC growth via mitochondrial stress-induced autophagy and apoptosis.Scientific reports · 2026Article
- RKIP regulates bone marrow macrophage differentiation to mediate osteoclastogenesis and H-type vessel formation.Nature communications · 2025Article
- Geniposide ameliorates cholesterol accumulation and promotes osteoblast differentiation by mediating the GLP-1R/AMPK/SREBP2 pathway.Journal of orthopaedic surgery and research · 2025Article
- Exploring causal correlations between inflammatory response-related genes and osteoporosis: a Multi-Omics Mendelian Randomization Study.Archives of medical science : AMS · 2025Article
- Combined metformin and simvastatin therapy inhibits SREBP2 maturation and alters energy metabolism in glioma.Cell death & disease · 2024Article
- S1P regulates intervertebral disc aging by mediating endoplasmic reticulum-mitochondrial calcium ion homeostasis.JCI insight · 2024Article
- The unfolded protein response regulates ER exit sites via SNRPB-dependent RNA splicing and contributes to bone development.The EMBO journal · 2024Article
- Fantastic voyage: The journey of NLRP3 inflammasome activation.Genes & diseases · 2024Review
- Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy.Cell communication and signaling : CCS · 2024Review
- In vivo therapy of osteosarcoma using anion transporters-based supramolecular drugs.Journal of nanobiotechnology · 2024Article
- Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases.Military Medical Research · 2023Review
- Article
- Bone and the Unfolded Protein Response: In Sickness and in Health.Calcified tissue international · 2023Review
- ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review.Biomolecules · 2023Review
- Hedgehog signaling regulates bone homeostasis through orchestrating osteoclast differentiation and osteoclast-osteoblast coupling.Cellular and molecular life sciences : CMLS · 2023Article
- The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling.International journal of biological sciences · 2023Article
- Antioxidant PDA-PEG nanoparticles alleviate early osteoarthritis by inhibiting osteoclastogenesis and angiogenesis in subchondral bone.Journal of nanobiotechnology · 2022Article
- Sigma-1 receptor attenuates osteoclastogenesis by promoting ER-associated degradation of SERCA2.EMBO molecular medicine · 2022Article
- Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis.Frontiers in molecular biosciences · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
Site-1 protease (S1P) is a Golgi-located protein that activates unique membrane-bound latent transcription factors, and it plays an indispensable role in endoplasmic reticulum stress, lipid metabolism, inflammatory response and lysosome function. A patient with S1P mutation exhibits severe skeletal dysplasia with kyphoscoliosis, dysmorphic facial features and pectus carinatum. However, whether S1P regulates bone remodeling by affecting osteoclastogenesis remains elusive. Here, we show that S1P is indeed a positive regulator of osteoclastogenesis. S1P ablation in mice led to significant osteosclerosis compared with wild-type littermates. Mechanistically, S1P showed upregulated during osteoclastogenesis and was identified as a direct target of miR-9-5p. S1P deletion in bone marrow monocytes (BMMs) inhibited ATF6 and SREBP2 maturation, which subsequently impeded CHOP/SREBP2-complex-induced LC3 expression and autophagy flux. Consistently, transfection of LC3 adenovirus evidently rescued osteoclastogenesis in S1P-deficient BMMs. We then identified the interaction regions between CHOP and SREBP2 by Co-immunoprecipitation (Co-IP) and molecular docking. Furthermore, S1P deletion or inhibitor efficaciously rescued ovariectomized (OVX)- and LPS-induced bone loss in vivo. Collectively, we showed that S1P regulates osteoclast differentiation in a LC3 dependent manner and so is a potential therapy target for osteoporosis.
Indexed as
Identifiers
What OpenQuestion holds
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.