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Purification and Biological Function of Caldecrin.

Akito Tomomura1, Kenjiro Bandow1, Mineko Tomomura2

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Caldecrin, a pancreatic protease, reduces serum calcium by inhibiting osteoclast differentiation and bone resorption. This multifunctional protein shows potential therapeutic applications for skeletal and inflammatory diseases.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • Blood calcium homeostasis is vital for biological functions.
  • Caldecrin, a chymotrypsin-like elastase from the pancreas, was identified as a serum calcium-decreasing factor.
  • Its activity requires trypsin-mediated activation, but structural processing is also essential.

Purpose of the Study:

  • To investigate the mechanisms by which caldecrin affects serum calcium levels and bone metabolism.
  • To explore caldecrin's role in osteoclast differentiation and function.
  • To assess caldecrin's potential as a therapeutic agent for skeletal and inflammatory conditions.

Main Methods:

  • Studied caldecrin's effect on osteoclast differentiation from bone marrow macrophages (BMMs) in vitro.
  • Investigated caldecrin's impact on mature osteoclast bone resorption.
  • Analyzed caldecrin's influence on lipopolysaccharide (LPS)-induced macrophage polarization.
  • Evaluated caldecrin's efficacy in vivo using ovariectomized and dystrophic mouse models.

Main Results:

  • Caldecrin suppresses osteoclast differentiation by inhibiting RANKL-induced NF-κB signaling and calcium oscillations.
  • It inhibits mature osteoclast bone resorption by affecting calcium entry and actin ring formation.
  • Caldecrin suppresses LPS-induced osteoclast formation and M1 macrophage polarization via TREM2.
  • In vivo studies demonstrated caldecrin's ability to prevent bone resorption and muscle destruction.

Conclusions:

  • Caldecrin is a unique multifunctional protease with significant anti-osteoclastogenic and anti-inflammatory properties.
  • Its mechanisms involve intricate signaling pathways regulating calcium homeostasis and immune responses.
  • Caldecrin represents a promising therapeutic target for skeletal disorders and inflammatory diseases.