局部应用骨形态发生蛋白-2（BMP-2）或转化生长因子-β1（TGF-β1）对关节软骨组成和骨赘形成的不同影响。

Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation.

作者信息

van Beuningen H M, Glansbeek H L, van der Kraan P M, van den Berg W B

机构信息

Department of Rheumatology, University Hospital Nijmegen, The Netherlands.

出版信息

Osteoarthritis Cartilage. 1998 Sep;6(5):306-17. doi: 10.1053/joca.1998.0129.

DOI:10.1053/joca.1998.0129

PMID:10197165

Abstract

OBJECTIVE

The related molecules bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-beta 1) have both been shown to stimulate chondrocyte proteoglycan (PG) synthesis in vitro. We investigated the in-vivo effects of these factors on articular cartilage PG metabolism.

DESIGN

Several doses of BMP-2 or TGF-beta 1 were injected into the murine knee joint, once or repeatedly. Patellar cartilage PG synthesis was measured by [35S]-sulfate incorporation and reverse transcriptase polymerase chain reaction (RT-PCR). PG content was analyzed by measuring safranin O staining intensity on histologic sections.

RESULTS

A single injection of 200 ng BMP-2 induced a much earlier and more impressive stimulation of articular cartilage PG synthesis, than 200 ng TGF-beta 1. RT-PCR revealed that both factors upregulated mRNA of aggrecan more than that of biglycan and decorin. However, 21 days after a single injection of 200 ng TGF-beta 1 PG synthesis still was significantly increased, while stimulation by BMP-2 only lasted for 3 to 4 days. Stimulation by BMP-2 could be prolonged to at least 2 weeks by triple injections of 200 ng each, at alternate days. Remarkably, even after this intense exposure to BMP-2, stimulation of PG synthesis was not reflected in long-lasting enhancement of PG content of articular cartilage. In contrast, even a single injection with 200 ng of TGF-beta 1 induced prolonged enhancement of PG content. After repeated injections, both BMP-2 and TGF-beta 1 induced chondrogenesis at specific sites. 'Chondrophytes' induced by BMP-2 were found predominantly in the region where the growth plates meet the joint space, while those triggered by TGF-beta 1 originated from the periosteum also at sites remote from the growth plates.

CONCLUSIONS

BMP-2 and TGF-beta stimulate PG synthesis and PG content with different kinetics, and these factors have different chondro-inductive properties.

摘要

目的

相关分子骨形态发生蛋白-2（BMP-2）和转化生长因子β-1（TGF-β1）在体外均已显示能刺激软骨细胞蛋白聚糖（PG）合成。我们研究了这些因子对关节软骨PG代谢的体内作用。

设计

将几剂BMP-2或TGF-β1注射到小鼠膝关节，单次或重复注射。通过[35S] - 硫酸盐掺入和逆转录酶聚合酶链反应（RT-PCR）测量髌软骨PG合成。通过测量组织学切片上番红O染色强度分析PG含量。

结果

单次注射200 ng BMP-2比200 ng TGF-β1更早且更显著地刺激关节软骨PG合成。RT-PCR显示，这两种因子上调聚集蛋白聚糖的mRNA比双糖链蛋白聚糖和核心蛋白聚糖更多。然而，单次注射200 ng TGF-β1后21天PG合成仍显著增加，而BMP-2的刺激仅持续3至4天。通过每隔一天注射三次各200 ng，BMP-2的刺激可延长至至少2周。值得注意的是，即使在如此强烈暴露于BMP-2之后，PG合成的刺激并未反映在关节软骨PG含量的持久增加上。相反，即使单次注射200 ng TGF-β1也诱导PG含量的持久增加。重复注射后，BMP-2和TGF-β1均在特定部位诱导软骨形成。由BMP-2诱导的“软骨细胞”主要在生长板与关节间隙相遇的区域发现，而由TGF-β1触发的那些也起源于远离生长板部位的骨膜。