Effects of chronic growth hormone and insulin-like growth factor 1 deficiency on osteoarthritis severity in rat knee joints
Effects of chronic growth hormone and insulin-like growth factor 1 deficiency on osteoarthritis severity in rat knee joints
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DOI：
10.1002/art.22254
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发表时间：
2006-12-01
影响因子：
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通讯作者：
Carlson, Cathy S.
中科院分区：
文献类型：
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作者：
Ekenstedt, Kari J.;Sonntag, William E.;Carlson, Cathy S.
目标。确定生长激素（GH）和胰岛素样生长因子1 （IGF-1）慢性缺乏对骨关节炎（OA）严重程度的影响。方法。35只大鼠在4周龄时分为4个治疗组：1个对照组（正常GH/1GF-1水平[杂合]）和3个基因突变导致GH缺乏的侏儒组。第一组侏儒接受生长激素64周（生长激素充足），第二组接受生长激素至14周龄，随后接受生理盐水治疗50周（成人发病的生长激素/IGF-1缺乏症[AO-GHD]）。第三个侏儒组只接受生理盐水注射（终生生长激素缺乏[GHD]）。对膝关节内侧腔室切片进行分级和组织学测量；采用因子分析对数据进行总结，采用方差分析和体重调整对治疗效果进行评价。结果。治疗对终末IGF-1水平和体重有显著影响（P = 0.002和P < 0.001）。因子分析共得到5个因素，其中前3个因素不受治疗的显著影响。因子4（以胫骨平台内侧关节软骨宽度和面积加权）受治疗影响显著（P < 0.012）， AO-GHD组大于GHD组（P < 0.05）。因子5（主要由关节软骨结构和甲苯胺蓝染色损失评分加权）也受到治疗的显著影响（P < 0.001），并且GH充满组的因子5（病变较轻）明显低于所有其他治疗组（P < 0.05）。尽管存在软骨病变，但在GH/ igf -1缺陷的动物中未观察到骨赘和软骨下硬化。结论。这些结果表明，慢性GH/IGF-1缺乏导致骨性关节炎关节软骨病变的严重程度增加，而没有骨性病变。
Objective. To determine the effects of chronic deficiency of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) on osteoarthritis (OA) severity. Methods. Thirty-five rats were divided into 4 treatment groups at 4 weeks of age: 1 control group (normal GH/1GF-1 levels [heterozygous]) and 3 groups of dwarves with a genetic mutation that results in GH deficiency. The first dwarf group received GH for 64 weeks (GH replete) and the second received GH until 14 weeks of age, followed by saline for 50 weeks (adult-onset GH/IGF-1 deficiency [AO-GHD]). The third dwarf group received saline injections only (lifetime GH deficient [GHD]). Sections of the medial knee joint compartment were graded and measured histologically; data were summarized using factor analysis, and treatment effects were assessed using analysis of variance and adjusting for body weight. Results. Terminal IGF-1 levels and body weights were significantly affected by treatment (P = 0.002 and P < 0.001, respectively). Factor analysis yielded a total of 5 factors, the first 3 of which were not significantly affected by treatment. Factor 4 (weighted by medial tibial plateau articular cartilage width and area) was significantly affected by treatment (P < 0.012), with larger values in the AO-GHD group than in the GHD group (P < 0.05). Factor 5 (weighted primarily by articular cartilage structure and loss of toluidine blue staining scores) also was significantly affected by treatment (P < 0.001), and was significantly lower (less severe lesions) in the GH replete group than in all other treatment groups (P < 0.05). Despite the presence of cartilage lesions, osteophytes and subchondral sclerosis were not observed in GH/IGF-1-deficient animals. Conclusion. These results indicate that chronic GH/IGF-1 deficiency causes an increased severity of articular cartilage lesions of OA without the bony lesions normally seen in this disease.