Abstract
The assay for the carboxyterminal telopeptide of type I collagen, ICTP, has
been
shown to be a reliable marker in many pathological conditions but insensitive to
changes in physiological bone turnover. This has induced uncertainty and
confusion regarding the role of ICTP assay in the study of collagen metabolism in
bones. Especially, since another assay for the carboxyterminal telopeptide of
type I collagen, serum CrossLaps ELISA, sensitively follows the changes in
physiological bone turnover. To find out the reasons for the discrepancy we
characterized the antigenic determinant of the ICTP assay by comparing human and
bovine antigens after trypsin and chymotrypsin treatments. An assay for bovine
ICTP was developed contemporarily with the present study. The epitope lies on the
phenylalanine rich region of two telopeptide chains. We were able to show that
the region is destroyed by cathepsin K, an osteoclastic enzyme responsible for
physiological bone turnover, but not by several matrix metalloproteinases (MMPs),
which are important collagen degrading enzymes in pathological conditions.
Cathepsin K treatment had no effect on the CrossLaps assay. The CrossLaps assay
is also able to measure the MMP-derived fragments, but usually their amount is so
low in serum that it is masked by the cathepsin K-derived collagen degradation.
The results explain the apparent discrepancy regarding the different behaviour of
ICTP and CrossLaps assays in various conditions as also verified in our study
with rheumatoid arthritis patients.
The ICTP assay was also found to measure only trivalently cross-linked
forms
of the carboxyterminal telopeptide which contains two telopeptide chains, and is
therefore unable to react with divalently or histidinohydroxylysinonorleucine
(HHL)-cross-linked forms of the carboxyterminal telopeptide. These forms can be
measured with the SP4 (synthetic peptide 4) assay. We utilized this property in
analyzing the skin samples of 18 breast cancer patients on both the irradiated
and unirradiated side. The content of HHL was increased on the irradiated side,
as were type I collagen synthesis and degradation.
In conclusion, there are two assays for two different degradation products
of the
trivalently cross-linked carboxyterminal telopeptide of type I collagen, ICTP and
CrossLaps, the former measuring the MMP-derived and the latter the cathepsin
K-derived collagen degradation.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-6491-6 |
| Date | 03 August 2001 |
| Creators | Sassi, M.-L. (Mirja-Liisa) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2001 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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