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ResearchIn-Press PreviewBone biologyCell biology Open Access | 10.1172/JCI168155
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Xue, P. in: JCI | PubMed | Google Scholar
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Zhang, W. in: JCI | PubMed | Google Scholar |
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Shen, M. in: JCI | PubMed | Google Scholar
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Yang, J. in: JCI | PubMed | Google Scholar |
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Chu, J. in: JCI | PubMed | Google Scholar
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Wang, S. in: JCI | PubMed | Google Scholar
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Wan, M. in: JCI | PubMed | Google Scholar
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Zheng, J. in: JCI | PubMed | Google Scholar
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Qiu, Z. in: JCI | PubMed | Google Scholar |
1Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
2Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, United States of America
3Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, China
4Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States of America
5Department of biomedical engineering, Johns Hopkins University School of Medicine, Baltimore, United States of America
Find articles by Cao, X. in: JCI | PubMed | Google Scholar
Published August 28, 2024 - More info
Chronic low back pain (LBP) can severely affect daily physical activity. Aberrant osteoclast-mediated resorption leads to porous endplates for the sensory innervation to cause LBP. Here, we report that the expression of proton-activated chloride (PAC) channel is induced during osteoclast differentiation in the porous endplates via a RANKL-NFATc1 signaling pathway. Extracellular acidosis evokes robust PAC currents in osteoclasts. An acidic environment of porous endplates and elevated PAC activation-enhanced osteoclast fusion provoke LBP. Further, we find that genetic knockout of PAC gene Pacc1 significantly reduces endplate porosity and spinal pain in a mouse LBP model, but it does not affect bone development or homeostasis of bone mass in adult mice. Moreover, both osteoclast bone resorptive compartment environment and PAC traffic from the plasma membrane to endosomes to form an intracellular organelle Cl channel have low pH around 5.0. The low pH environment activates PAC channel to increase sialyltransferase St3gal1 expression and sialylation of TLR2 in initiation of osteoclast fusion. Aberrant osteoclast-mediated resorption is also found in most skeletal disorders, including osteoarthritis, ankylosing spondylitis, rheumatoid arthritis, heterotopic ossification, enthesopathy. Thus, elevated Pacc1 expression and PAC activity could be a potential therapeutic target for LBP and osteoclast-associated pain.