ArticleThe Journal of clinical investigation2024
Proton-activated chloride channel increases endplate porosity and pain in a mouse spine degeneration model.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed.
- Dorsal horn DCC amplification loop induced by endplate osteoclasts generates chronic nociplastic low back pain in male mice.Nature communications · 2026Article
- Mobilizing stem cells and inhibition of autoimmunity synergistically modify autoimmune disease to relieve pain: a potential MRG-001 therapy for rheumatoid arthritis.International journal of surgery (London, England) · 2026Article
- CFTR mediates ClNature communications · 2026Article
- Proton-activated chloride channel 1 is essential for innate host defense against bacterial sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- PTH induced osteoblast Slit3 to decrease aberrant sensory innervation in degenerated vertebral endplates to relieve low back pain in mice.Bone research · 2026Article
- GDF15 induces excessive activation of osteoclasts within the vertebral endplates leading to early endplate degeneration.JCI insight · 2026Article
- Targeting Osteoclastogenesis: Sabutoclax reduces tumor-associated osteolysis and tumor burden within the bone microenvironment.American journal of cancer research · 2026Article
- Up-regulation of peripheral and central CGRP expression combined with subchondral bone remodeling in rat MIA-induced TMJOA model.Journal of oral & facial pain and headache · 2025Article
- GPR65 Functions as a Key Factor of Bone Aging and a Novel Therapeutic Target for Osteoporosis.Aging cell · 2025Article
- Article
- Aberrant bone formation and dysregulated bone homeostasis in ankylosing spondylitis.World journal of stem cells · 2025Article
- Alternative splicing regulates PACC1 function and promotes acidosis-induced cytotoxicity.Frontiers in cell and developmental biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Chronic low back pain (LBP) can severely affect daily physical activity. Aberrant osteoclast-mediated resorption leads to porous endplates, which allow the sensory innervation that causes LBP. Here, we report that expression of the proton-activated chloride (PAC) channel was induced during osteoclast differentiation in the porous endplates via a RANKL/NFATc1 signaling pathway. Extracellular acidosis evoked robust PAC currents in osteoclasts. An acidic environment of porous endplates and elevated PAC activation-enhanced osteoclast fusion provoked LBP. Furthermore, we found that genetic knockout of the PAC gene Pacc1 significantly reduced endplate porosity and spinal pain in a mouse LBP model, but it did not affect bone development or homeostasis of bone mass in adult mice. Moreover, both the osteoclast bone-resorptive compartment environment and PAC traffic from the plasma membrane to endosomes to form an intracellular organelle Cl channel had a low pH of approximately 5.0. The low pH environment activated the PAC channel to increase sialyltransferase St3gal1 expression and sialylation of TLR2 in the initiation of osteoclast fusion. Aberrant osteoclast-mediated resorption is also found in most skeletal disorders, including osteoarthritis, ankylosing spondylitis, rheumatoid arthritis, heterotopic ossification, and enthesopathy. Thus, elevated Pacc1 expression and PAC activity could be a potential therapeutic target for the treatment of LBP and osteoclast-associated pain.
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.