Related Experiment Video
Updated: Feb 22, 2026
A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro
Published on: June 16, 2022
Conditional deletion of CD98hc inhibits osteoclast development
Hideki Tsumura1, Morihiro Ito2, Masamichi Takami3
1Division of Laboratory Animal Resources, National Research Institute for Child Health and Development, Tokyo, Japan.
Insights
The CD98 heavy chain (CD98hc) is crucial for osteoclast formation, impacting both integrin signaling and amino acid transport pathways. Impaired CD98hc function severely hinders multinucleated osteoclast development.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- The CD98 heavy chain (CD98hc) is known to regulate cell fusion and amino acid transport.
- Osteoclast formation is essential for bone remodeling and is a complex cellular process.
Purpose of the Study:
- To investigate the specific role of CD98hc in osteoclastogenesis.
- To elucidate the molecular mechanisms by which CD98hc influences osteoclast formation.
Main Methods:
- Utilized CD98hc-deficient (CD98hcflox/floxLysM-cre) and wild-type peritoneal macrophages.
- Co-cultured macrophages with osteoblasts in the presence of 1,25(OH)2 vitamin D3.
- Assessed osteoclast formation via tartrate-resistant acid phosphatase staining and analyzed signaling pathways (ERK, Akt, JNK, p130Cas) and the GCN pathway.
Main Results:
- Osteoclast formation was significantly impaired in CD98hc-deficient macrophages compared to wild-type.
- CD98hc deficiency suppressed M-CSF-RANKL-induced phosphorylation of key signaling molecules (ERK, Akt, JNK, p130Cas).
- RANKL stimulation induced the general control non-derepressible (GCN) pathway in CD98hc-deficient macrophages, indicating activation by amino acid starvation.
Conclusions:
- CD98hc plays a dual role in osteoclast formation by mediating integrin signaling and regulating amino acid transport.
- These findings highlight CD98hc as a critical regulator in the development of osteoclasts.
Abstract:
The CD98 heavy chain (CD98hc) regulates virus-induced cell fusion and monocyte fusion, and is involved in amino acid transportation. Here, we examined the role that CD98hc plays in the formation of osteoclasts using CD98hcflox/floxLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH)2 vitamin D3, and thereafter stained with tartrate-resistant acid phosphatase staining solution. The multinucleated osteoclast formation was severely impaired in the peritoneal macrophages isolated from the CD98hc-defect mice compared with those from wild-type mice. CD98hc mediates integrin signaling and amino acid transport through the CD98 light chain (CD98lc). In integrin signaling, suppression of the M-CSF-RANKL-induced phosphorylation of ERK, Akt, JNK and p130Cas were observed at the triggering phase in the CD98h-defect peritoneal macrophages. Moreover, we showed that the general control non-derepressible (GCN) pathway, which was activated by amino acid starvation, was induced by the CD98hc-defect peritoneal macrophages stimulated with RANKL. These results indicate that CD98 plays two important roles in osteoclast formation through integrin signaling and amino acid transport.
Related Concept Videos
01:31Osteoclasts in Bone Remodeling
02:34Inhibition of Cdk Activity
01:01Regulation of Hematopoietic Stem Cells