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Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
Published on: September 13, 2017
Acidic microenvironment created by osteoclasts causes bone pain associated with tumor colonization
Maho Nagae1, Toru Hiraga, Toshiyuki Yoneda
1Department of Biochemistry, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan. tyoneda@dent.osaka-u.ac.jp
Journal of Bone and Mineral Metabolism
|February 27, 2007
Summary
Cancer-induced bone pain may stem from an acidic environment created by osteoclasts. Bisphosphonates (BPs) reduced this pain and the expression of acid-sensing channels (ASICs) in a rat model, suggesting a link between acidosis and bone pain.
Area of Science:
- Oncology
- Pain Research
- Cell Biology
Background:
- Bone pain is a common complication in cancer patients with bone metastases.
- Osteoclasts, involved in bone resorption, create an acidic microenvironment by secreting protons.
- Acidosis is a known cause of pain, suggesting a role in cancer-related bone pain.
Purpose of the Study:
- To investigate if an acidic microenvironment created by osteoclasts contributes to bone pain in cancer metastasis.
- To examine the effect of bisphosphonates (BPs) on pain and related molecular changes in a bone metastasis model.
Main Methods:
- An animal model using MRMT-1 rat breast cancer cells inoculated into rat tibiae to induce hyperalgesia.
- Radiographic, histological, and behavioral analyses to assess bone destruction and pain.
- Immunohistochemistry and mRNA expression analysis of acid-sensing receptors (ASICs, TRPV1) in dorsal root ganglia (DRGs) and spinal cord.
Main Results:
- MRMT-1 cells induced significant bone destruction and hyperalgesia, with increased osteoclast numbers.
- Zoledronic acid (ZOL), a BP, significantly reduced hyperalgesia and decreased c-Fos expression in spinal cord neurons.
- ZOL treatment also reduced the expression of ASIC1a and ASIC1b in ipsilateral DRGs.
Conclusions:
- Osteoclast-driven acidosis contributes to cancer-induced bone pain (hyperalgesia).
- This pain mechanism involves the upregulation of acid-sensing channels (ASICs), specifically ASIC1a and ASIC1b.
- Bisphosphonates may alleviate bone pain by targeting the acidic microenvironment and ASIC expression.
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