Differential expression of human lysyl hydroxylase genes, lysine hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro

被引:124
作者
Uzawa, K
Grzesik, WJ
Nishiura, T
Kuznetsov, SA
Robey, PG
Brenner, DA
Yamauchi, M
机构
[1] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Med, Div Digest Dis, Chapel Hill, NC USA
[3] NIDR, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA
关键词
D O I
10.1359/jbmr.1999.14.8.1272
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The pattern of lysyl hydroxylation in the nontriple helical domains of collagen is critical in determining the cross-linking pathways that are tissue specific. We hypothesized that the tissue specificity of type I collagen cross-linking is, in part, due to the differential expression of lysyl hydroxylase genes (Procollagen-lysine,2-oxyglutarate,5-dioxygenase 1, 2, and 3 [PLOD1, PLOD2, and PLOD3]), In this study, we have examined the expression patterns of these three genes during the course of in vitro differentiation of human osteoprogenitor cells (bone marrow stromal cells [BMSCs]) and normal skin fibroblasts (NSFs), In addition, using the medium and cell layer/matrix fractions in these cultures, lysine hydroxylation of type I collagen or chains and collagen cross-linking chemistries have been characterized, High levels of PLOD1 and PLOD3 genes were expressed in both BMSCs and NSFs, and the expression levels did not change in the course of differentiation. In contrast to the PLOD1 and PLOD3 genes, both cell types showed low PLOD2 gene expression in undifferentiated and early differentiated conditions. However, fully differentiated BMSCs, but not NSFs, exhibited a significantly elevated level (6-fold increase) of PLOD2 mRNA, This: increase coincided with the onset of matrix mineralization and with the increase in lysyl hydroxylation in the nontriple helical domains of at chains of type I collagen molecule. Furthermore, the collagen cross-links that are derived from the nontriple helical hydroxylysine-aldehyde were found only in fully differentiated BMSC cultures. The data suggests that PLOD2 expression is associated with lysine hydroxylation in the nontriple helical domains of collagen and, thus, could be partially responsible for the tissue-specific collagen cross-linking pattern.
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页码:1272 / 1280
页数:9
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