ArticleThe Journal of clinical investigation1989
Cytoplasmic pH regulation and chloride/bicarbonate exchange in avian osteoclasts.
Article in The Journal of clinical investigation, 1989. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 131 citations in OpenAlex.
- Promoting Bone Health in Layer Chickens from the Perspective of Mitochondrial Energy Metabolism in Osteoclasts.Animals : an open access journal from MDPI · 2026Review
- Biosynthesis of reveromycin derivatives by altering the regioselectivity of cytochrome P450revI.Chemical science · 2025Article
- Membrane Transport Proteins in Osteoclasts: The Ins and Outs.Frontiers in cell and developmental biology · 2021Review
- Targeting the pH Paradigm at the Bedside: A Practical Approach.International journal of molecular sciences · 2020Review
- Investigating Osteocytic Perilacunar/Canalicular Remodeling.Current osteoporosis reports · 2019Review
- Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility.eLife · 2018Article
- Article
- Chloride-hydrogen antiporters ClC-3 and ClC-5 drive osteoblast mineralization and regulate fine-structure bone patterning in vitro.Physiological reports · 2015Article
- Extracellular fluid flow and chloride content modulate H(+) transport by osteoclasts.BMC cell biology · 2015Article
- Development of an in vitro cell system from zebrafish suitable to study bone cell differentiation and extracellular matrix mineralization.Zebrafish · 2013Article
- SLC4A2-mediated Cl-/HCO3- exchange activity is essential for calpain-dependent regulation of the actin cytoskeleton in osteoclasts.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- RNA therapeutics targeting osteoclast-mediated excessive bone resorption.Advanced drug delivery reviews · 2012Review
- High capacity Na+/H+ exchange activity in mineralizing osteoblasts.Journal of cellular physiology · 2011Article
- A novel role for Stat1 in phagosome acidification and natural host resistance to intracellular infection by Leishmania major.PLoS pathogens · 2009Article
- Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Advances in osteoclast biology resulting from the study of osteopetrotic mutations.Human genetics · 2009Review
- HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Molecular biology of bone remodelling.Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases · 2008Article
- Osteoclasts: what do they do and how do they do it?The American journal of pathology · 2007Article
- Mechanisms balancing skeletal matrix synthesis and degradation.The Biochemical journal · 2002Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Osteoclasts resorb bone by first attaching to the bone surface and then secreting protons into an isolated extracellular compartment formed at the cell-bone attachment site. This secretion of protons (local acidification) is required to solubilize bone hydroxyapatite crystals and for activity of bone collagen-degrading acid proteases. However, the large quantity of protons required, 2 mol/mol of calcium, would result in an equal accumulation of cytosolic base equivalents. This alkaline load must be corrected to maintain cytosolic pH within physiologic limits. In this study, we have measured cytoplasmic pH with pH-sensitive fluorescent compounds, while varying the extracellular ionic composition of the medium, to determine the nature of the compensatory mechanism used by osteoclasts during bone resorption. Our data show that osteoclasts possess a chloride/bicarbonate exchanger that enables them to maintain normal intracellular pH in the face of a significant proton efflux. This conclusion follows from the demonstration of a dramatic cytoplasmic acidification when osteoclasts that have been incubated in bicarbonate-containing medium are transferred into bicarbonate-free medium. This acidification is absolutely dependent on and proportional to medium [Cl-]. Furthermore, acidification is inhibited by the classic inhibitor of red cell anion exchange, 4,4'-diisothiocyanatostilbene-2,2'-disulfonate, and by diphenylamine-2-carboxylate, an inhibitor of chloride specific channels. However, the acidification process is neither energy nor sodium dependent. The physiologic importance of chloride/bicarbonate exchange is demonstrated by the chloride dependence of recovery from an endogenous or exogenous alkaline load in osteoclasts. We conclude that chloride/bicarbonate exchange is in large part responsible for cytoplasmic pH homeostasis of active osteoclasts, showing that these cells are similar to renal tubular epithelial cells in their regulation of intracellular pH.
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.