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首页> 外文期刊>Osteoarthritis and cartilage >Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO(4)).
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Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO(4)).

机译：葡萄糖胺（GlcN），N-乙酰基GlcN（GlcNAc）GlcN硫酸盐（GlcN.S）和共价硫酸葡萄糖胺（GlcN-SO（4））对关节软骨细胞增殖和阴离子糖缀合物合成的调节。

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OBJECTIVES: To investigate, in chondrocyte cultures under conditions for maximizing responses in proliferation and proteoglycan (PG) synthesis, the effects of glucosamine hydrochloride (GlcN.HCl) and glucosamine sulfate (GlcN.S) salts, N-acetyl glucosamine (GlcNAc), and covalently substituted GlcN-X,Y,Z(SO(4))(n) (general formula). METHODS: Bovine articular chondrocytes (BAC) were studied under anchorage-independent (AI, alginate beads) and anchorage-dependent (AD, plastic surface) conditions. Differentiation markers were evaluated (e.g., cartilage-specific (V+C)(-) fibronectin). Varying concentrations of GlcN.HCl, GlcN.S, GlcNAc and GlcN sulfated at positions -2, -3, -6, (-2,3), (-3,6) and (-3,4,6), were tested. Cell proliferation, DNA synthesis and [(35)S]-sulfate incorporation into newly synthesized PG were determined. RESULTS: Increasing GlcN.HCl or GlcN.S concentrations gave decreasing net PG synthesis. Compounds showed more pronounced effects in AD cultures (expressing the V(-)C(+) fibronectin isoform) compared to AI cultures ((V+C)(-) isoform). Addition of GlcN.HCl or GlcN.S gave a concentration-dependent decrease in BAC proliferation, partially prevented by glucose (Glc). GlcNAc was not inhibitory. Addition of GlcN-2-SO(4) or GlcN-2,6-diSO(4) did not affect proliferation or DNA synthesis. The other GlcN-sulfates gave varying inhibitory effects, which for GlcN-3-SO(4) were reversed by inosine. CONCLUSIONS: The free amino group of GlcN seems responsible for inhibition of chondrocyte proliferation and PG synthesis. These effects were greater under higher concentrations of GlcN in AD vs AI conditions. GlcN.HCl behaves similarly to GlcN.S, but differential effects with GlcN-X,Y,Z(SO(4))(n) isomers were observed. Acetylation or sulfation of the GlcN amino group reverses or partially reverses, respectively, anti-proliferative effects of GlcN. Sulfation of GlcN, at positions 3 and 6 results in complex effects on AC proliferation and PG synthesis.
机译：目的：研究软骨细胞在最大化增殖和蛋白聚糖（PG）合成反应的条件下的培养情况，研究了氨基葡萄糖盐酸盐（GlcN.HCl）和氨基葡萄糖硫酸盐（GlcN.S）盐，N-乙酰基氨基葡萄糖（GlcNAc）的影响，和共价取代的GlcN-X，Y，Z（SO（4））（n）（通式）。方法：在不依赖于锚定（AI，藻酸盐珠）和依赖于锚定（AD，塑料表面）的条件下研究了牛关节软骨细胞（BAC）。评估分化标志物（例如，软骨特异性（V + C）（-）纤连蛋白）。在-2，-3，-6，（-2,3），（-3,6）和（-3,4,6）位置上硫酸化的GlcN.HCl，GlcN.S，GlcNAc和GlcN的浓度分别为经过测试。确定细胞增殖，DNA合成和[（35）S]硫酸盐纳入新合成的PG。结果：增加GlcN.HCl或GlcN.S浓度会降低净PG合成。与AI培养物（（V + C）（-）亚型）相比，化合物在AD培养物中表现出更明显的作用（表达V（-）C（+）纤连蛋白同工型）。 GlcN.HCl或GlcN.S的添加使BAC增殖呈浓度依赖性降低，部分被葡萄糖（Glc）阻止。 GlcNAc没有抑制作用。 GlcN-2-SO（4）或GlcN-2,6-diSO（4）的添加不会影响增殖或DNA合成。其他GlcN硫酸盐产生不同的抑制作用，肌苷对GlcN-3-SO（4）的抑制作用相反。结论：GlcN的游离氨基似乎是抑制软骨细胞增殖和PG合成的原因。与AI条件相比，AD和GlcN浓度较高时，这些影响更大。 GlcN.HCl的行为类似于GlcN.S，但观察到GlcN-X，Y，Z（SO（4））（n）异构体的差异作用。 GlcN氨基的乙酰化或硫酸化分别逆转或部分逆转了GlcN的抗增殖作用。位置3和6处GlcN的硫酸化对AC增殖和PG合成产生复杂影响。

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