Calpain-6, a Target Molecule of Glucocorticoids, Regulates Osteoclastic Bone Resorption via Cytoskeletal Organization and Microtubule Acetylation
2011

Calpain-6 and Its Role in Bone Resorption

Sample size: 6 publication 10 minutes Evidence: high

Author Information

Author(s): Hong Jung Min, Teitelbaum Steven L, Kim Tae-Ho, Ross F Patrick, Kim Shin-Yoon, Kim Hyun-Ju

Primary Institution: Kyungpook National University Hospital

Hypothesis

Does calpain-6 influence osteoclast function and cytoskeletal organization in response to glucocorticoids?

Conclusion

Calpain-6 regulates cytoskeletal organization and microtubule stability in osteoclasts, and its inhibition may mediate the resorption-arresting properties of glucocorticoids.

Supporting Evidence

  • Calpain-6 is suppressed 12-fold by dexamethasone in osteoclasts.
  • Overexpression of Capn6 promotes osteoclast spreading and actin ring formation.
  • Capn6 knockdown impairs cytoskeletal organization and resorptive capacity.
  • Microtubule stability and acetylation are suppressed in DEX-treated osteoclasts.
  • Capn6 overexpression rescues GC-mediated disruption of osteoclast cytoskeleton.

Takeaway

Calpain-6 helps bone cells called osteoclasts maintain their shape and function, and when it's blocked by certain medications, these cells can't do their job properly.

Methodology

Primary bone marrow-derived macrophages were cultured and treated with RANKL and M-CSF to differentiate into osteoclasts, followed by various assays to assess cytoskeletal organization and bone resorption.

Limitations

The study primarily focuses on in vitro models, which may not fully replicate in vivo conditions.

Participant Demographics

C57/BL6 mice, 6- to 8-week-old.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1002/jbmr.241

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