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TRPV1, ASICs and P2X2/3 expressed in bone cells simultaneously regulate bone metabolic markers in ovariectomized mice
1Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
Objectives:
Nociceptors are expressed at peripheral terminals of neurons. Recent studies have shown that TRPV1, a nociceptor, is expressed in bone tissue and regulates bone metabolism. We have demonstrated that a TRPV1 antagonist improved pain-like behavior in ovariectomized (OVX) mice. The aim of this study was to determine whether nociceptors, including TRPV1, acid-sensing ion channel (ASIC) and P2X2/3 are expressed in bone cells, and to examine the effects of nociceptor antagonists on bone metabolism.
Methods:
The expression of nociceptors in femoral bone tissue and cultured bone marrow cells in OVX and sham-operated mice were examined. The effects of nociceptor antagonists on the up-regulated expression of bone metabolic markers, Runx2, Osterix, osteocalcin and RANKL, were also examined.
Results:
TRPV1, ASIC 2 and 3, and P2X2 and 3, were expressed in bone tissue and bone marrow cells, and the expression levels of ASIC1 and 2, and P2X2 were significantly increased in OVX mice in comparison with those in sham mice. Treatment with nociceptor antagonists significantly inhibited the expression of bone metabolic markers in OVX mice.
Conclusion:
An array of nociceptors, TRPV1, ASICs and P2X2/3, could simultaneously regulate not only increases in skeletal pain but also bone turnover in OVX mice.
Insights
Nociceptors like TRPV1 are found in bone cells and influence bone metabolism. Blocking these nociceptors, including acid-sensing ion channels (ASICs) and P2X2/3 receptors, reduced bone metabolic markers in ovariectomized mice.
Area of Science:
- Bone Biology
- Neuroscience
- Pain Research
Background:
- Nociceptors, involved in pain sensation, are increasingly recognized for roles beyond pain.
- Transient Receptor Potential Vanilloid 1 (TRPV1) is a nociceptor found in bone, impacting skeletal metabolism.
- Ovariectomy (OVX) in mice leads to altered bone metabolism and pain-like behaviors.
Purpose of the Study:
- To investigate the expression of nociceptors (TRPV1, ASICs, P2X2/3) in bone cells.
- To determine the effect of nociceptor antagonists on bone metabolism markers in OVX mice.
Main Methods:
- Examined nociceptor expression in femoral bone and bone marrow cells from OVX and sham-operated mice.
- Assessed the impact of nociceptor antagonists on key bone metabolic markers (Runx2, Osterix, osteocalcin, RANKL).
Main Results:
- TRPV1, ASIC 2/3, and P2X2/3 were expressed in bone and bone marrow cells.
- Expression of ASIC1/2 and P2X2 was elevated in OVX mice compared to sham controls.
- Nociceptor antagonist treatment significantly suppressed the expression of bone metabolic markers in OVX mice.
Conclusions:
- Multiple nociceptors, including TRPV1, ASICs, and P2X2/3, are present in bone cells.
- These nociceptors appear to regulate both skeletal pain and bone turnover, particularly in the context of OVX.
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