Livne E, Laufer D, Blumenfeld I
Division of Morphological Sciences, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9649, 31096 Haifa, Israel.
Calcif Tissue Int. 1997 Jul;61(1):62-7. doi: 10.1007/s002239900296.
In several aspects the features of aging resemble those of the state of growth hormone (GH) deficiency. Alterations of bone density and increased incidence of osteoporosis are some of the characteristics of aging that are similar to the findings in GH-deficient adults. Osteoarthritis (OA), a nonfatal condition predominating in old age, is characterized by the slowly progressive destruction of articular cartilage of joints. OA lesions are observed in the temporomandibular joint of ICR mice aged 7 months and older. The aim of the present study was to compare the response of chondrocytes from mandibular condyle cartilage of young and old mice to GH and to ascertain whether chondrocytes of old animals could still be stimulated to proliferate and to synthesize matrix components under the direct effect of GH in vitro. Mandibular condyles from young (3-month-old) and old (20-month-old) female ICR mice were cultured up to 72 hours in the presence of recombinant rat GH (0.1-100 ng/ml). 3H-Thymidine and 35S-sulfate were introduced during the last 24 hours of culture. Administration of GH appeared to increase only slightly the incorporation of 3H-thymidine in cartilage from young compared with the response in cartilage from old animals which was much more significant at 24 hours and 48 hours in culture. The same pattern was seen for the effect of GH on the incorporation of 35S-sulfate. Cartilage from young animals responded only slightly to GH, whereas a significant response was observed in cartilage from old animals after 24 and 48 hours in vitro. DNA contents were significantly elevated at all time intervals in both old and young animals, yet more significantly in cultures from old animals. In contrast, the activities of both alkaline and acid phosphatases were elevated at all time intervals in cultures from young animals, whereas no induction was observed in cultures from old animals. Tissue sections from cultures of old animals treated with GH (10 ng/ml, 48 hours) revealed atypical hypertrophic cells along the articular surface and also dark staining along the cartilage-bone interface. Exposure to tetracycline (10 mg/ml, 24 hours) resulted in an induced fluorescence, indicating enhanced mineralization in this region. Results of this study indicate that mandibular condyle cartilage from OA old mice responds in vitro to the addition of GH via anabolic activities of cell proliferation, sulfated proteoglycan synthesis, and possibly enhanced mineralization.
在几个方面，衰老的特征与生长激素（GH）缺乏状态的特征相似。骨密度改变和骨质疏松症发病率增加是衰老的一些特征，这些特征与GH缺乏的成年人的表现相似。骨关节炎（OA）是一种在老年人群中占主导地位的非致命性疾病，其特征是关节软骨的缓慢进行性破坏。在7个月及以上的ICR小鼠的颞下颌关节中观察到OA病变。本研究的目的是比较年轻和老年小鼠下颌髁突软骨细胞对GH的反应，并确定老年动物的软骨细胞在体外GH的直接作用下是否仍能被刺激增殖并合成基质成分。将年轻（3个月大）和老年（20个月大）雌性ICR小鼠的下颌髁突在重组大鼠GH（0.1 - 100 ng/ml）存在的情况下培养72小时。在培养的最后24小时加入3H - 胸腺嘧啶核苷和35S - 硫酸盐。与老年动物软骨的反应相比，GH给药似乎仅略微增加了年轻动物软骨中3H - 胸腺嘧啶核苷的掺入，在培养24小时和48小时时，老年动物软骨的反应更为显著。GH对35S - 硫酸盐掺入的影响也呈现相同模式。年轻动物的软骨对GH反应轻微，而老年动物的软骨在体外培养24小时和48小时后观察到显著反应。老年和年轻动物在所有时间间隔的DNA含量均显著升高，但老年动物培养物中的升高更为显著。相反，年轻动物培养物中碱性和酸性磷酸酶的活性在所有时间间隔均升高，而老年动物培养物中未观察到诱导作用。用GH（10 ng/ml，48小时）处理的老年动物培养物的组织切片显示沿关节表面有非典型肥大细胞，并且在软骨 - 骨界面也有深色染色。暴露于四环素（10 mg/ml，24小时）导致诱导荧光，表明该区域矿化增强。本研究结果表明，OA老年小鼠的下颌髁突软骨在体外通过细胞增殖、硫酸化蛋白聚糖合成以及可能增强的矿化等合成代谢活动对添加的GH作出反应。
