期刊
CALCIFIED TISSUE INTERNATIONAL
卷 106, 期 2, 页码 194-207出版社
SPRINGER
DOI: 10.1007/s00223-019-00618-w
关键词
ELISA; Osteoclast; Acp5; Bone resorption; Biomarker
资金
- Karolinska Institute
- Marie Curie Initial Training Network (Euroclast, FP7-People-2013-ITN) [607447]
- ERC FP7 Health-2007-A
- Loo and Hans Osterman foundation
- Maud Kuistila Memorial foundation
- Jane and Aatos Erkko foundation
- Swedish Research Council [K2015-99X-10363-23-4, 2017-01083]
- Marie Curie Alumni Association
- Swedish Research Council [2017-01083] Funding Source: Swedish Research Council
Tartrate-resistant acid phosphatase type 5 (TRAP) exists as two isoforms, 5a and 5b. 5b is a marker of osteoclast number and 5a of chronic inflammation; however, its association with bone resorption is unknown. In this study, a double-TRAP 5a/5b sandwich ELISA measuring 5a and 5b protein in the same sample was developed. TRAP 5a and 5b protein levels were evaluated as osteoclast differentiation/activity markers in serum and in culture, and their correlation to the resorption marker CTX-I was examined. Serum TRAP 5a and 5b concentrations in healthy men were 4.4 +/- 0.6 ng/ml and 1.3 +/- 0.2 ng/ml, respectively, and they correlated moderately to each other suggesting that their secretion is coupled under healthy conditions. A correlation was also observed between serum TRAP 5a and 5b with CTX-I, suggesting that both TRAP isoforms associate with osteoclast number. During osteoclast differentiation on plastic/bone, predominantly 5b increased in media/lysate from M-CSF/RANKL-stimulated CD14+ PBMCs. However, substantial levels of 5a were detected at later stages suggesting that both isoforms are secreted from differentiating OCs. More TRAP 5b was released on bone indicating a connection to osteoclast resorptive activity, and a peak in TRAP 5b/5a-ratio coincided with rapid CTX-I release. At the end of the culture period of M-CSF + RANKL-stimulated CD14+ PBMCs, there was a correlation between the secretion of TRAP 5a and 5b proteins with CTX-I. The correlation of not only 5b but also 5a with collagen degradation, both in serum and osteoclast cultures indicates that a considerable proportion of the TRAP 5a originates from osteoclasts and may reflect a hitherto undisclosed regulatory mechanism during bone resorption and bone remodeling.
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