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Updated: Jun 6, 2026
Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
Published on: March 18, 2019
Antibodies against ClC7 inhibit extracellular acidification-induced Cl⁻ currents and bone resorption activity in
Kimiko Ohgi1, Fujio Okamoto, Hiroshi Kajiya
1Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Japan.
Abstract:
The Cl⁻ channel/transporter ClC7 is crucial for osteoclastic bone resorption and might become a therapeutic target for osteoporosis. In this study, we raised anti-ClC7 polyclonal antibodies against three different peptide sequences, including G215, P249, and R286, which are the mutation regions found in autosomal dominant osteopetrosis type II patients and examined the effects of these antibodies on the ClC7 Cl⁻ current induced by extracellular acidification (acid-activated Cl⁻ current) using the whole-cell patch clamp technique and bone resorption activity in mouse osteoclasts. Intracellular dialysis of osteoclasts with antibodies to intracellular G215 (Ab-G215) and extracellular application of antibodies to extracellular P249 (Ab-P249) or R286 (Ab-R286) inhibited the acid-activated Cl⁻ current. These antibodies also suppressed the acid-activated Cl⁻ current in ClC7 overexpressing Raw264.7 cells; however, Cl⁻ currents evoked by hypotonic stimulation and the inherent inwardly rectifying K+ currents in mouse osteoclasts were unaffected by these antibodies. Furthermore, extracellularly applied Ab-P249 and Ab-R286 also reduced bone resorption activity. Our results demonstrate that these antibodies specifically block ClC7 in mouse osteoclasts. Thus, anti-ClC7 antibodies have potential promise for treatment of osteoporosis.
Insights
New antibodies targeting the ClC7 chloride channel show promise for treating osteoporosis. These antibodies specifically block ClC7 function in osteoclasts, reducing bone resorption activity.
Area of Science:
- Biochemistry
- Physiology
- Molecular Biology
Background:
- Chloride channel 7 (ClC7) is vital for osteoclast bone resorption.
- Dysfunctional ClC7 is implicated in autosomal dominant osteopetrosis type II.
- ClC7 represents a potential therapeutic target for osteoporosis.
Purpose of the Study:
- To develop and evaluate anti-ClC7 antibodies for therapeutic potential.
- To investigate the effects of anti-ClC7 antibodies on ClC7 channel activity.
- To assess the impact of anti-ClC7 antibodies on osteoclast bone resorption.
Main Methods:
- Generation of polyclonal antibodies against ClC7 peptide sequences (G215, P249, R286).
- Whole-cell patch clamp electrophysiology to measure Cl⁻ currents in mouse osteoclasts and Raw264.7 cells.
- Assay of bone resorption activity in mouse osteoclasts.
Main Results:
- Antibodies targeting intracellular G215 (Ab-G215) and extracellular P249 (Ab-P249) or R286 (Ab-R286) inhibited acid-activated Cl⁻ currents.
- These antibodies specifically suppressed ClC7-mediated currents, not other ion currents.
- Extracellular antibodies (Ab-P249, Ab-R286) significantly reduced osteoclast bone resorption activity.
Conclusions:
- Developed antibodies specifically block ClC7 chloride channel function in osteoclasts.
- Anti-ClC7 antibodies demonstrate potential for treating osteoporosis by inhibiting bone resorption.
- Targeting ClC7 with antibodies offers a promising therapeutic strategy for bone diseases.
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