Evidence map›Paper›PMID 41148822›Full record

ReviewCells2025

Joint Acidosis and Acid-Sensing Receptors and Ion Channels in Osteoarthritis Pathobiology and Therapy.

William N Martin, Colette Hyde, Adam Yung, Ryan Taffe, Bhakti Patel, Ajay Premkumar, Pallavi Bhattaram, Hicham Drissi, Nazir M Khan

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

William N MartinDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.ORCID 0000-0002-6023-8198
Colette HydeDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.
Adam YungDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.
Ryan TaffeDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.
Bhakti PatelDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.
Ajay PremkumarDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.
Pallavi BhattaramDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.
Hicham DrissiDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.
Nazir M KhanDepartment of Orthopaedics, Emory Musculoskeletal Institute, Emory University, Atlanta, GA 30329, USA.

Funding

Targeting GPR68 as a novel modulator of osteoarthritisR03TR003669 · NCATS · EMORY UNIVERSITY · PI KHAN, MOHD NAZIR · 2022 to 2022
$128k
NCATS NIH HHS R03 TR003669NIH HHS 1R03TR003669-22RRD VA I50 RX004845
6 · The paper itself

Abstract

Osteoarthritis (OA) lacks disease-modifying therapies, in part because key features of the joint microenvironment remain underappreciated. One such feature is localized acidosis, characterized by sustained reductions in extracellular pH within the cartilage, meniscus, and the osteochondral interface despite near-neutral bulk synovial fluid. We synthesize current evidence on the origins, sensing, and consequences of joint acidosis in OA. Metabolic drivers include hypoxia-biased glycolysis in avascular cartilage, cytokine-driven reprogramming in the synovium, and limits in proton/lactate extrusion (e.g., monocarboxylate transporters (MCTs)), with additional contributions from fixed-charge matrix chemistry and osteoclast-mediated acidification at the osteochondral junction. Acidic niches shift proteolysis toward cathepsins, suppress anabolic control, and trigger chondrocyte stress responses (calcium overload, autophagy, senescence, apoptosis). In the nociceptive axis, protons engage ASIC3 and sensitize TRPV1, linking acidity to pain. Joint cells detect pH through two complementary sensor classes: proton-sensing GPCRs (GPR4, GPR65/TDAG8, GPR68/OGR1, GPR132/G2A), which couple to G

Indexed as

AcidosisAcid Sensing Ion ChannelsIon ChannelsJointsOsteoarthritisAnimalsChondrocytesHumansAcid Sensing Ion ChannelsIon ChannelsacidosisASICcathepsin Kextracellular pHGPR4GPR68/OGR1lactateosteoarthritispH-responsive deliveryTRPV1

Identifiers

PMID41148822
PMCPMC12563613

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.