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Caldecrin: A pancreas-derived hypocalcemic factor, regulates osteoclast formation and function.
Mineko Tomomura1, Akito Tomomura1
1Mineko Tomomura, Meikai Pharmaco-Medical Laboratory, MPL and Division of Biochemistry, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
Caldecrin, a pancreatic protease, effectively inhibits bone resorption and osteoclast formation. This unique enzyme shows therapeutic potential for treating bone diseases like osteoporosis.
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Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Caldecrin, a serine protease from the pancreas, exhibits chymotrypsin-like activity and belongs to the elastase family.
- Initially identified for its calcium-lowering effects, its role in bone metabolism was further investigated.
Purpose of the Study:
- To explore the anti-osteoclastogenic and bone resorption inhibitory activities of caldecrin.
- To elucidate the mechanisms underlying caldecrin's effects on bone metabolism, independent of its protease activity.
Main Methods:
- In vivo studies using ovariectomized mice to assess caldecrin's effect on bone resorption.
- In vitro experiments using fetal mouse long bone organ cultures and bone marrow cells to analyze caldecrin's impact on osteoclastogenesis and activity.
- Investigating the RANKL-stimulated signaling pathways affected by caldecrin.
Main Results:
- Ectopic caldecrin expression prevented bone resorption in vivo.
- Caldecrin inhibited parathyroid hormone-stimulated calcium release and suppressed osteoclast formation by interfering with the RANKL-stimulated pathway.
- Caldecrin also inhibited mature osteoclast bone resorption by preventing RANKL-stimulated Src activation and actin ring formation.
Conclusions:
- Caldecrin is a multifunctional protease with significant anti-osteoclastogenic activities, distinct from its protease function.
- Caldecrin demonstrates potential as a therapeutic agent for osteolytic diseases such as osteoporosis and osteoarthritis.

