ArticleCell death and differentiation2023
HSC70 mediated autophagic degradation of oxidized PRL2 is responsible for osteoclastogenesis and inflammatory bone destruction.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.Biochemical Society transactions · 2026Review
- Chaperone-Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microautophagy: current understanding of its molecular mechanisms and functions.Autophagy reports · 2026Review
- Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1/Th17 cell apoptosis in inflammatory bowel disease.Gut microbes · 2025Article
- Targeting chaperone-mediated autophagy to regulate osteoclast activity as a therapeutic strategy for osteoporosis.Materials today. Bio · 2025Article
- Impact of reactive oxygen species on bone regeneration in diabetes: Mechanisms and therapeutic strategies.Redox biology · 2025Review
- Antler stem cell-derived exosomes restore periodontal homeostasis in a rat model with diabetic periodontitis through enhancing ROS scavenging and osteogenesis.Cell death discovery · 2025Article
- Effects of chloroquine and hydroxychloroquine on bone health (Review).Molecular medicine reports · 2025Review
- PRL2 negatively regulates FcεRI mediated activation of mast cells.Cell death & disease · 2025Article
- Resetting the Hsc70-mediated lysosomal degradation of PD-L1 via a supramolecular meso peptide for the restoration of acquired anti-tumor T cell immunity.Journal of nanobiotechnology · 2025Article
- Autophagy: regulating the seesaw of bone-fat balance.Frontiers in cell and developmental biology · 2025Review
- Advances in Functionalized Nanoparticles for Osteoporosis Treatment.International journal of nanomedicine · 2025Review
- The Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging.Aging and disease · 2024Review
- Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.Zoological research · 2024Article
- PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury.Nature communications · 2024Article
- Activation of Chaperone-Mediated Autophagy Inhibits the Aryl Hydrocarbon Receptor Function by Degrading This Receptor in Human Lung Epithelial Carcinoma A549 Cells.International journal of molecular sciences · 2023Article
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation leads to systemic osteoporosis or local bone destruction, however, the underlying molecular mechanisms are still poorly understood. In this study, we report that PRL2 is a negative regulator of osteoclastogenesis and bone absorption. Mice with PRL2 deficiency exhibit a decrease in bone volume and an increase in osteoclast numbers. PRL2 negatively regulates RANKL-induced reactive oxygen species production through the activation of RAC1, thus PRL2 deficient osteoclast precursors have both increased osteoclast differentiation ability and bone resorptive capacity. During inflammation, oxidized PRL2 is a selected substrate of HSC70 and conditions of oxidative stress trigger rapid degradation of PRL2 by HSC70 mediated endosomal microautophagy and chaperone-mediated autophagy. Ablation of PRL2 in mouse models of inflammatory bone disease leads to an increase in the number of osteoclasts and exacerbation of bone damage. Moreover, reduced PRL2 protein levels in peripheral myeloid cells are highly correlated with bone destruction in a mouse arthritis model and in human rheumatoid arthritis, while the autophagy inhibitor hydroxychloroquine blocked inflammation-induced PRL2 degradation and bone destruction in vivo. Therefore, our findings identify PRL2 as a new regulator in osteoimmunity, providing a link between inflammation and osteoporosis. As such, PRL2 is a potential therapeutic target for inflammatory bone disease and inhibition of HSC70 mediated autophagic degradation of PRL2 may offer new therapeutic tools for the treatment of inflammatory bone disease.
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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.