ArticleThe American journal of pathology2005
Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 154 citations in OpenAlex.
- Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin.BMC clinical pharmacology · 2008Trial
- Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: the effect of water and timing of meal intake on oral delivery of Salmon Calcitonin.BMC clinical pharmacology · 2008Trial
- Acid-responsive metal organic frameworks with photothermal effects for osteoarthritis multiple therapy.RSC advances · 2026Article
- EnhancedACS applied bio materials · 2025Article
- Osteoclast-derived coupling factors: origins and state-of-play Louis V Avioli lecture, ASBMR 2023.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Caffeine regulates both osteoclast and osteoblast differentiation via the AKT, NF-κB, and MAPK pathways.Frontiers in pharmacology · 2024Article
- Effect of Omeprazole on Fracture Healing in the Random-Patterned Rat Tibial Fracture Model: An Experimental Study.Journal of clinical practice and research · 2023Article
- Neutralization of Intracellular pH Homeostasis to Inhibit Osteoclasts Based on a Spatiotemporally Selective Delivery System.Nano letters · 2023Article
- Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases.Biomedicines · 2022Article
- Serum biomarkers for bisphosphonate-related osteonecrosis of the jaw: a prospective clinical study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Article
- Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation.Frontiers in cell and developmental biology · 2022Review
- DI-5-Cuffs: Bone Remodelling and Associated Metabolism Markers in Humans After Five Days of Dry Immersion to Simulate Microgravity.Frontiers in physiology · 2022Article
- Lonafarnib Inhibits Farnesyltransferase via Suppressing ERK Signaling Pathway to Prevent Osteoclastogenesis in Titanium Particle-Induced Osteolysis.Frontiers in pharmacology · 2022Article
- Physiologic osteoclasts are not sufficient to induce skeletal pain in mice.European journal of pain (London, England) · 2021Article
- Influence of Gestational Hormones on the Bacteria-Induced Cytokine Response in Periodontitis.Mediators of inflammation · 2021Review
- Enhanced Activation of Rac1/Cdc42 and MITF Leads to Augmented Osteoclastogenesis in Autosomal Dominant Osteopetrosis Type II.JBMR plus · 2019Article
- Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes.Arthritis research & therapy · 2018Article
- Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rats [corrected].American journal of translational research · 2017Article
- Real-time intravital imaging of pH variation associated with osteoclast activity.Nature chemical biology · 2016Article
- Effects of rabeprazole on bone metabolic disorders in a gastrectomized rat model.Biomedical reports · 2016Article
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibition of bone resorption without inhibition of bone formation. We investigated the role of acidification in human osteoclastic resorption and life span in vitro using inhibitors of chloride channels (NS5818/NS3696), the proton pump (bafilomycin) and cathepsin K. We found that bafilomycin and NS5818 dose dependently inhibited acidification of the osteoclastic resorption compartment and bone resorption. Inhibition of bone resorption by inhibition of acidification, but not cathepsin K inhibition, augmented osteoclast survival, which resulted in a 150 to 300% increase in osteoclasts compared to controls. We investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ovariectomy model with twice daily oral dosing of NS3696 at 50 mg/kg for 6 weeks. We observed a 60% decrease in resorption (DPYR), increased tartrate-resistant acid phosphatase levels, and no effect on bone formation evaluated by osteocalcin. We speculate that attenuated acidification inhibits dissolution of the inorganic phase of bone and results in an increased number of nonresorbing osteoclasts that are responsible for the coupling to normal bone formation. Thus, we suggest that acidification is essential for normal bone remodeling and that attenuated acidification leads to uncoupling with decreased bone resorption and unaffected bone formation.
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