title: [The mechanism of TRACP 5b maturation].
abstract: Serum tartrate resistant acid phosphatase 5b (TRACP 5b) is an isozyme of osteoclast origin. Indeed, measurement of TRACP 5b activity is used as an index of osteoclast activity. However, the precise mechanism of TRACP 5b maturation is unclear. This study aimed to clarify the mechanism of generation of TRACP 5b. We used a highly sensitive fiber-type DNA chip to investigate the mechanism of generation of TRACP 5b at the genetic level. Genes derived from three related cell types (monocytes, macrophages and osteoclasts) were compared. In addition, at the protein level, posttranscriptional modification was tested by Western blotting using an antiserum specific for the flexible loop region of TRACP 5. Our DNA chip study shows that genes implicated in oligosaccharide construction do not show significant differences in expression levels between the cell types under investigation. Strongly expressed Cathepsin K was observed in osteoclasts. Western blotting demonstrated that TRACP undergoes unique partial degradation during bone resorption, such that serum TRACP 5b lacks the flexible loop found in TRACP 5a. In conclusion, TRACP 5b generated by a specific posttranscriptional modification pathway undergoes partial digestion in resorption lacunae or inside osteoclasts. Serum TRACP 5b lacking the flexible loop differs from TRACP 5a in terms of optimum pH, isoelectric point, sugar chain and antigenicity. The measurement of TRACP 5b could therefore be of great use for monitoring of osteoporosis, rheumatoid arthritis and bone metastasis.
authors.affiliation: Biochemical Laboratory, Nittobo Boseki Co., Ltd. Kohriyama 963-8061.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohashi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ichimura
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Toshihide
authors.initials: T
authors.lastname: Miura
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Wataru
authors.initials: W
authors.lastname: Ohashi
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Sato
authors.forename: Ryo
authors.initials: R
authors.lastname: Kojima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Katayama
authors.forename: Takami
authors.initials: T
authors.lastname: Miki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D000135:Acid Phosphatase / Q000096:biosynthesis*; D015153:Blotting, Western; D001862:Bone Resorption / Q000503:physiopathology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase