期刊
JOURNAL OF CELL BIOLOGY
卷 149, 期 4, 页码 983-993出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.149.4.983
关键词
endochondral ossification; hypertrophic cartilage; skeletogenesis; marrow; lymphopenia
类别
资金
- NIAMS NIH HHS [AR43362] Funding Source: Medline
A variable skeleto-hematopoietic phenotype was observed in collagen X null mice which mirrored the defects in transgenic (Tg) mice with dominant interference collagen X mutations (Jacenko, O., P. LuValle, and B.R. Olsen, 1993, Nature. 365:56-61). Specifically, perinatal lethality was seen in similar to 10.8% of null mutants at week three after birth, and in another subset by 12 wk, In perinatal lethal mutants, growth plates were compressed, trabecular bone reduced, and hematopoietic aplasia and erythrocyte-filled vascular sinusoids were apparent in marrows, Lymphatic organs, reduced to similar to 80% that of controls, displayed altered architecture and lymphocyte content. In thymuses, a paucity of cortical CD3(+)/CD4(+)/CD8(+) lymphocytes was consistent with the marrow's inability to replenish maturing T cells. In spleens, an unaltered T cell distribution was coupled with diffuse staining for IgD(+)/B220(+) B cells, whose reduction was prominent in poorly organized lymphatic nodules. Disorderly arrays of splenic macrophages surrounding periarteriolar lymphatic sheaths and a red pulp depletion further complemented the Tg perinatal lethal phenotype, Moreover, subtle growth plate compressions and hematopoietic changes were seen in all null mice. Data from Tg and null mice implicate the disruption of collagen X function in the observed skeleto-hematopoietic defects, and suggest that hypertrophic cartilage and endochondral skeletogenesis may contribute to the marrow microenvironment prerequisite for blood cell differentiation.
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