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Purification and Biological Function of Caldecrin

1
Division of Biochemistry, Department of Oral Biology & Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan
2
Department of Oral Health Sciences, Meikai University School of Health Sciences, 1-1 Akemi, Urayasu, Chiba 279-8550, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Basil D. Roufogalis
Received: 29 May 2021 / Revised: 16 July 2021 / Accepted: 19 July 2021 / Published: 23 July 2021
Blood calcium homeostasis is critical for biological function. Caldecrin, or chymotrypsin-like elastase, was originally identified in the pancreas as a serum calcium-decreasing factor. The serum calcium-decreasing activity of caldecrin requires the trypsin-mediated activation of the protein. Protease activity-deficient mature caldecrin can also reduce serum calcium concentration, indicating that structural processing is necessary for serum calcium-decreasing activity. Caldecrin suppresses the differentiation of bone-resorbing osteoclasts from bone marrow macrophages (BMMs) by inhibiting receptor activator of NF-κB ligand (RANKL)-induced nuclear factor of activated T-cell cytoplasmic 1 expression via the Syk–PLCγ–Ca2+ oscillation-calcineurin signaling pathway. It also suppresses mature osteoclastic bone resorption by RANKL-stimulated TRAF6–c-Src–Syk–calcium entry and actin ring formation. Caldecrin inhibits lipopolysaccharide (LPS)-induced osteoclast formation in RANKL-primed BMMs by inducing the NF-κB negative regulator A20. In addition, caldecrin suppresses LPS-mediated M1 macrophage polarization through the immunoreceptor triggering receptor expressed on myeloid cells (TREM) 2, suggesting that caldecrin may function as an anti-osteoclastogenic and anti-inflammatory factor via TREM2. The ectopic intramuscular expression of caldecrin cDNA prevents bone resorption in ovariectomized mice, and the administration of caldecrin protein also prevents skeletal muscle destruction in dystrophic mice. In vivo and in vitro studies have indicated that caldecrin is a unique multifunctional protease and a possible therapeutic target for skeletal and inflammatory diseases. View Full-Text
Keywords: calcium metabolism; bone metabolism; protease; osteoclast; macrophage; RANKL; LPS; TLR4; TREM2 calcium metabolism; bone metabolism; protease; osteoclast; macrophage; RANKL; LPS; TLR4; TREM2
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MDPI and ACS Style

Tomomura, A.; Bandow, K.; Tomomura, M. Purification and Biological Function of Caldecrin. Medicines 2021, 8, 41. https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080041

AMA Style

Tomomura A, Bandow K, Tomomura M. Purification and Biological Function of Caldecrin. Medicines. 2021; 8(8):41. https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080041

Chicago/Turabian Style

Tomomura, Akito, Kenjiro Bandow, and Mineko Tomomura. 2021. "Purification and Biological Function of Caldecrin" Medicines 8, no. 8: 41. https://0-doi-org.brum.beds.ac.uk/10.3390/medicines8080041

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