The role of myostatin in chicken (Gallus domesticus) myogenic satellite cell proliferation and differentiation

Myostatin (GDF-8) inhibits the activation, proliferation, and differentiation of myogenic satellite cells. The relative importance of this growth factor is demonstrated in myostatin-null mice and cattle possessing defective myostatin genes. These defects result in greatly enhanced musculature. In the present study, the effect of myostatin on chicken myogenic satellite cells derived from two different skeletal muscles was studied. The effect of anti-myostatin antibodies on cellular responses was also examined. Satellite cells isolated from the pectoralis major (PM) muscles were more responsive to the proliferation depressing effects of myostatin compared to cells from the biceps femoris (BF; P or=0.05). Myostatin administered to proliferating cells depressed the synthesis of decorin (P Decorin expression in PM cells was unchanged (P>or= 0.05). Administration of anti-myostatin antibodies to proliferating cultures increased cell proliferation by 6-7% over 3 days. There was no effect on differentiation of either PM or BF cells. The present study demonstrates that there are differences in the responsiveness to myostatin of chicken satellite cells derived from different muscles. Evidence is also given to support the role of endogenous myostatin in autocrine regulation of muscle growth.     

饰胶蛋白聚糖的抗纤维化和抗肿瘤作用

饰胶蛋白聚糖（Decorin，DCN）属富含亮氨酸小分子蛋白多糖家族成员之一。大量证据表明：DCN通过结合并中和转化生长因子-β（TGF-β），干扰其与受体结合所致的胞外基质过度沉积，以产生抗纤维化和抑制疤痕形成的作用；DCN亦通过激活EGFR／MAPK／p21信号通路和抑制EGF—EGFR介导的促细胞增殖信号通路等机制，抑制肿瘤细胞增殖与转移。基于DCN以上两方面的生物活性，加之源于人体自身产生，其重组产品免疫原性较低，提示DCN对于慢性纤维化和肿瘤等疾病的防治具有潜在的药用开发价值。     

Decorin mRNA和p57KIP2 mRNA在非小细胞肺癌中的表达及其临床意义

目的检测Decorin mRNA和p57~(KIP2) mRNA在非小细胞肺癌中的表达情况,并分析它们与非小细胞肺癌的病理、临床特征及预后的关系。方法选取石蜡包埋的59例非小细胞肺癌及12例癌旁正常肺组织的标本制作组织芯片。利用原位杂交法检测Decorin mRNA和p57~(KIP2) mRNA的表达情况。结果Decorin mRNA在癌旁正常肺组织和非小细胞肺癌组织中的表达率分别为66.7%(8/12)和20.3%(12/59),正常组织中Decorin mRNA的表达高于肺癌组织(P<0.05)。大细胞肺癌中Decorin mRNA的表达高于鳞癌(P<0.05)。鳞癌中p57~(KIP2) mRNA的阳性表达率为63.2%(12/19),高于腺癌、大细胞癌和小细胞癌(P<0.05)。在无淋巴结转移的非小细胞肺癌标本中Decorin mRNA和p57~(KIP2) mRNA的表达呈增高趋势,与有淋巴结转移的标本比较其差异具有统计学意义。Decorin mRNA和p57~(KIP2) mRNA的表达无相关性(P>0.05)。结论Decorin和p57~(KIP2)的表达可能与非小细胞肺癌的组织学类型和转移有关,有望成为监测非小细胞肺癌患者病情发展及评价预后的有用指标。     

Stimulation of Small Proteoglycan Synthesis by the Hyaluronan Synthesis Inhibitor 4-Methylumbelliferone in Human Skin Fibroblasts

Human skin fibroblasts cultured with 4-methylumbelliferone (MU), a hyaluronan synthesis inhibitor, produce a hyaluronan-deficient extracellular matrix (See []). Our present study investigated the effects of MU on proteoglycan, which is the other main component of the extracellular matrix, and interacts with hyaluronan. Proteoglycans isolated from culture medium in the presence or absence of MU were characterized by gel-filtration chromatography, ion-exchange HPLC, electrophoresis, and immunoblotting. We found that MU had only a negligible effect on the synthesis of large proteoglycan but increased the production of small proteoglycan in comparison with cultures lacking MU. This small proteoglycan was identified by immunoblotting as decorin. The structures of decorin synthesized in the presence and absence of MU were compared by gel-filtration chromatography, and the data indicated that cells incubated with MU produced a larger decorin molecule than cells incubated without MU. Furthermore, the two decorins had galactosaminoglycan chains of different sizes. These results suggest that MU inhibits the synthesis of hyaluronan and accelerates production of the larger decorin in the extracellular matrix.     

Proteoglycans in Predentin: The Last 15 Micrometers Before Mineralization

Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization. In order to investigate the distribution and potential functions of decorin, biglycan (BGN), and fibromodulin (3 SLRPs, potentially related to dentinogenesis), we performed light and electron immunochemistry on teeth from rats, and on wild-type and biglycan knockout mice (BGN KO). Immunohistochemical data demonstrate that chondroitin sulfate/dermatan sulfate (CS/DS) and keratan sulfate (KS) distributions displayed reverse gradients in predentin. The decrease of CS/DS labeling from the proximal to the distal predentin contrasted with the sharp decorin increase observed in the distal predentin near the predentin/dentin transition, an effect possibly attributable to the deglycosylation action of stromelysin-1. In contrast, BGN concentration was apparently constant throughout the whole predentin. Additional immunolabelings showed, for the first time, the presence of fibromodulin in predentin. Compared with the wild-type mouse, the mean diameter of collagen fibrils in the BGN KO was smaller in the proximal predentin but larger in the central and distal predentin, the metadentin was broader, and the dentin mineralization appeared altered and heterogeneous. Altogether, our data suggest an important role for BGN in dentin formation and mineralization.     

Structural Change in Decorin with Skin Aging

Decorin, the main proteoglycan in skin, has a small size with a core protein of ～ 40kDa and one chondroitin sulfate/dermatan sulfate glycosaminoglycan (GAG) chain. The main function of decorin is to regulate the collagen matrix assembly. Decorin is distributed along collagen fibrils with the core protein and the decorin GAG chain controls the distance between the collagen fibrils. Reducing the length of the decorin GAG chain reduces the distance between the collagen fibrils. Age-related changes in decorin are apparent in the GAG chain in respect to the molecular size and sulfate position but not in the core protein. Structural changes in the decorin GAG chain may be involved in changes in collagen matrix assembly during the aging process.     

青少年特发性脊柱侧凸患者髂骨中双糖链蛋白多糖和核心蛋白聚糖的表达

目的:观察非胶原骨基质蛋白中双糖链蛋白多糖(Biglycan)和核心蛋白聚糖(Decorin)在青少年特发性脊柱侧凸(adolescentidiopathicscoliosis,AIS)患者髂骨中的表达情况。方法:从10例行后路自体骨融合的AIS女性患者(AIS组)和6例无骨代谢性疾病需行髂骨自体骨移植的其它骨科疾病女性患者(对照组)获取髂骨标本。AIS组患者年龄11.9￣19.1岁,平均14.9岁,Cobb角55°(45°￣61°);对照组平均年龄40.8岁。标本于10%缓冲福尔马林液中固定6h,在福尔马林酸中脱钙3周。切片厚度为5!m,行免疫组化染色。用半定量方法分析双糖链蛋白多糖和核心蛋白聚糖在单位视野骨细胞与骨基质中的表达。结果:AIS组髂骨中骨细胞与骨基质表达核心蛋白聚糖各6例,表达双糖链蛋白多糖各6例。对照组核心蛋白聚糖在骨细胞与骨基质中均为阳性表达;双糖链蛋白多糖在骨基质中均为阳性表达,在骨细胞中阳性表达5例。!2检验显示AIS组上述两种非胶原骨基质蛋白多糖的阳性表达率明显低于对照组(P<0.05)。结论:双糖链蛋白多糖和核心蛋白聚糖在AIS患者髂骨中的表达较对照组低,研究其在AIS患者骨骼中的表达和分布,有助于研究AIS的骨质密度和骨生长发育异常的分子基础,进一步认识该病的病因与发病机理。     

Decorin and glycosaminoglycan synthesis in skin fibroblasts from patients with systemic sclerosis

We investigated the expression of decorin and the synthesis of sulphated glycosaminoglycans (GAGs) in cultured fibroblasts from patients with early-stage systemic sclerosis (SSc). Decorin mRNA levels were 1.8-fold higher in SSc fibroblasts than in control fibroblasts. SSc fibroblasts also produced 2.3-fold more decorin core protein and 2.2-fold more sulphated GAGs including dermatan sulphate and chondroitin sulphate. Newly synthesized GAGs, in the presence of p -nitrophenyl β-xylopyranoside, which elongates dermatan sulphate and chondroitin sulphate as an initiator, were increased tenfold and were mainly composed of dermatan sulphate and chondroitin sulphate. The rate of stimulation by the β-xyloside was similar in SSc and control fibroblasts. These results suggest that the increased amount of dermatan/chondroitin sulphate in SSc fibroblasts reflects an enhanced expression of decorin core protein. Type I collagen mRNA levels in SSc fibroblasts were also increased together with its synthesis. Therefore, our results indicate that an altered decorin and collagen production may affect the organization of collagen fibres and the fibrotic process observed in patients with SSc. Received: 24 September 1996