Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees.
Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees.
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DOI：
10.1186/ar745
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发表时间：
2003
影响因子：
4.9
通讯作者：
Robbins PD
中科院分区：
文献类型：
--
作者：
Mi Z;Ghivizzani SC;Lechman E;Glorioso JC;Evans CH;Robbins PD
为了研究转化生长因子-β-1对软骨合成和其他关节病变的调节作用，我们用腺病毒介导的转化生长因子-β-1关节内基因转移的方法对幼稚和关节炎的兔膝关节进行了研究。将表达转化生长因子-β-1的腺病毒载体按递增剂量经膝腱注入正常兔膝关节和抗原性关节炎兔膝关节，对侧膝关节注射相同剂量的表达荧光素酶的腺病毒载体作为对照。关节腔内注射表达转化生长因子-β-1的腺病毒载体后，关节滑液中转化生长因子-β-1的表达呈剂量依赖性。在幼稚和关节炎兔膝关节中的关节内表达转化生长因子-β-1导致了兔膝关节和邻近肌肉组织的显著病理变化。转化生长因子-β-1升高引起的改变包括抑制白细胞的渗透，刺激糖胺多糖的释放和一氧化氮的产生，并诱导纤维化和肌肉水肿。此外，还观察到滑膜衬里内软骨生成的诱导。这些结果表明，尽管转化生长因子-β-1可能具有抗炎作用，但它不能刺激受损软骨的修复，甚至刺激软骨退化。因此，将转化生长因子-β-1基因转移到滑膜不适合用于治疗关节内病变。
To examine the effect of transforming growth factor (TGF)-β1 on the regulation of cartilage synthesis and other articular pathologies, we used adenovirus-mediated intra-articular gene transfer of TGF-β1 to both naïve and arthritic rabbit knee joints. Increasing doses of adenoviral vector expressing TGF-β1 were injected into normal and antigen-induced arthritis rabbit knee joints through the patellar tendon, with the same doses of an adenoviral vector expressing luciferase injected into the contralateral knees as the control. Intra-articular injection of adenoviral vector expressing TGF-β1 into the rabbit knee resulted in dose-dependent TGF-β1 expression in the synovial fluid. Intra-articular TGF-β1 expression in both naïve and arthritic rabbit knee joints resulted in significant pathological changes in the rabbit knee as well as in adjacent muscle tissue. The observed changes induced by elevated TGF-β1 included inhibition of white blood cell infiltration, stimulation of glycosaminoglycan release and nitric oxide production, and induction of fibrogenesis and muscle edema. In addition, induction of chondrogenesis within the synovial lining was observed. These results suggest that even though TGF-β1 may have anti-inflammatory properties, it is unable to stimulate repair of damaged cartilage, even stimulating cartilage degradation. Gene transfer of TGF-β1 to the synovium is thus not suitable for treating intra-articular pathologies.
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DOI：
10.1091/mbc.1.12.875
发表时间：
1990-11-01
期刊：
CELL REGULATION
影响因子：
--
作者：
SPORN, MB;ROBERTS, AB
通讯作者：
ROBERTS, AB
影响因子：
120.7
作者：
SPORN, MB;ROBERTS, AB
通讯作者：
ROBERTS, AB
DOI：
10.1006/bbrc.1994.1426
发表时间：
1994-04-15
影响因子：
3.1
作者：
TASKIRAN, D;STEFANOVICRACIC, M;EVANS, C
通讯作者：
EVANS, C
影响因子：
7
作者：
Bakker, AC;van de Loo, FAJ;van den Berg, WB
通讯作者：
van den Berg, WB
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ