Chondromodulin-I expression in the growth plate of young uremic rats

Authors: Amil, Benito; Fernandez-Fuente, Marta; Molinos, Ines; Rodriguez, Julian; Carbajo-Pérez, Eduardo; Garcia, Enrique; Yamamoto, Tadashi; Santos, Fernando

Source: Kidney International, Volume 66, Number 1, 1 July 2004 , pp. 51-59(9)

Publisher: Wiley-Blackwell

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Abstract:

Chondromodulin-I expression in the growth plate of young uremic rats.

Background. Growth retardation of chronic renal failure is associated with alterations in the growth plate suggestive of a disturbed chondrocyte maturation process and abnormal vascular invasion at the chondro-osseous interphase. Chondromodulin I (ChM-I) is a potent cartilage-specific angiostatic factor. Its pattern of expression in the uremic rat growth plate is unknown. Persistence of ChM-I synthesis and/or imbalance between ChM-I and vascular endothelial growth factor (VEGF) expressions might play a role in the alterations of uremic growth plate.

Methods. Growth cartilage ChM-I expression was investigated by immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) in growth-retarded young uremic rats (UREM), control rats, fed ad libitum (SAL) or pair-fed with the UREM group (SPF), and uremic rats treated with growth hormone (UREM-GH). VEGF expression was analyzed by immunohistochemistry.

Results. ChM-I and ChM-I mRNA were confined to the proliferative and early hypertrophic zones of growth cartilage. A similar number of chondrocytes per column was positive for ChM-I in the 4 groups. In accordance with the elongation of the hypertrophic stratum in uremia, the distance (X±SEM, μm) between the extracellular ChM-I signal and the metaphyseal end of growth cartilage was higher (P < 0.003) in UREM (236 ± 40) and UREM-GH (297 ± 17) than in SAL (92 ± 7) and SPF (113 ± 6). No differences in ChM-I expression were appreciated by RT-PCR. Similar VEGF positivity was observed in the hypertrophic chondrocytes of all groups.

Conclusion. In experimental uremia, expansion of growth cartilage does not result from increased or persistent expression of ChM-I or from reduced VEGF expression at the cartilage-metaphyseal bone interphase. GH treatment does not modify ChM-I and VEGF expressions.

Keywords: chondromodulin-I; chronic renal failure; growth plate; VEGF; growth hormone

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1523-1755.2004.00708.x

Publication date: 2004-07-01

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