title: Caldecrin: A pancreas-derived hypocalcemic factor, regulates osteoclast formation and function.
abstract: Caldecrin was originally isolated from the pancreas as a factor that reduced serum calcium levels. This secreted serine protease has chymotrypsin-like activity and is also known as chymotrypsin C; it belongs to the elastase family. Although intravenous administration of caldecrin decreases the serum calcium concentration even when its protease activity is blocked, this effect does require cleavage of caldecrin's pro-peptide by trypsin, converting it to the mature enzyme. Ectopic intramuscular expression of caldecrin prevented bone resorption in ovariectomized mice. Caldecrin inhibited parathyroid hormone-stimulated calcium release from fetal mouse long bone organ cultures. Furthermore, caldecrin suppressed the formation of osteoclasts from bone marrow cells by inhibiting the receptor activator of nuclear factor-κ B ligand (RANKL)-stimulated phospholipase Cγ-calcium oscillation-calcineurin-nuclear factor of activated T-cells, cytoplasmic 1 pathway. Caldecrin also suppressed the bone resorption activity of mature osteoclasts by preventing RANKL-stimulated Src activation, calcium entry, and actin ring formation. In vivo and in vitro studies have indicated that caldecrin is a unique multifunctional protease with anti-osteoclastogenic activities that are distinct from its protease activity. Caldecrin might be a potential therapeutic target for the treatment of osteolytic diseases such as osteoporosis and osteoarthritis. This mini-review describes caldecrin's historical background and its mechanisms of action.
authors.affiliation: Mineko 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.
authors.forename: Mineko
authors.initials: M
authors.lastname: Tomomura
authors.affiliation: Mineko 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.
authors.forename: Akito
authors.initials: A
authors.lastname: Tomomura
keywords: Bone resorption; Calcium signaling; Chymotrypsin; Hypocalcemia; Osteoclasts; Serine protease