Raloxifene ameliorates detrimental enzymatic and nonenzymatic collagen cross-links and bone strength in rabbits with hyperhomocysteinemia
Raloxifene ameliorates detrimental enzymatic and nonenzymatic collagen cross-links and bone strength in rabbits with hyperhomocysteinemia
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DOI：
10.1007/s00198-009-0980-4
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发表时间：
2010-04-01
影响因子：
4
通讯作者：
Shinohara, A.
中科院分区：
文献类型：
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作者：
Saito, M.;Marumo, K.;Shinohara, A.
我们证明了减少酶的二价未成熟和三价吡啶交联和增加非酶交联，戊糖苷（笔），在兔蛋氨酸（Met）诱导的高同型半胱氨酸血症。这种有害的骨交联的形成可通过雷洛昔芬（RLX）治疗得到改善。同型半胱氨酸（HCys）干扰胶原交联。由于RLX被认为可以改善骨质量，我们使用富含Met的饮食兔模型来研究RLX是否可以改善高同型半胱氨酸血症诱导的交联异常。（每组n = 6）：基线对照、假手术、假手术+1%Met饮食、卵巢切除术（OVX）、1%Met饮食+ OVX、OVX + RLX（10 mg/kg/天）和1%Met饮食+ OVX + RLX。RLX给药16周。我们测量了酶促未成熟和成熟的吡啶交联和非酶交联的量，Pen，并将交联含量与骨强度相关联。蛋氨酸饮食组中的HCys水平显著高于正常饮食组。有或无OVX的Met喂养的兔显示酶交联显著减少，而在有OVX的Met喂养的兔中观察到Pen增加。RLX处理Met喂养兔OVX的交联含量恢复到与假手术组相似的水平，同时骨强度得到改善，这些结果表明，高同型半胱氨酸血症通过减少酶交联和增加非酶交联降低骨强度。RLX可以改善高同型半胱氨酸血症诱导的有害的交联在兔OVX，并可能通过改善胶原交联提高骨强度。
We demonstrate a reduction in enzymatic divalent immature and trivalent pyridinium cross-links and an increase in the nonenzymatic cross-link, pentosidine (Pen), in rabbits with methionine (Met)-induced hyperhomocysteinemia. Such detrimental cross-link formation in bone was ameliorated by raloxifene (RLX) treatment.Collagen cross-links are determinants of bone quality. Homocysteine (Hcys) interferes with collagen cross-linking. Because RLX is thought to ameliorate bone quality, we investigated whether RLX ameliorated hyperhomocysteinemia-induced cross-link abnormalities using a Met-rich diet rabbit model.We divided New Zealand white rabbits into six groups (n = 6 per group): baseline control, sham operation, sham + 1% Met diet, ovariectomy (OVX), 1% Met diet + OVX, OVX + RLX (10 mg/kg/day), and 1% Met diet + OVX + RLX. RLX was administered for 16 weeks. We measured the amount of enzymatic immature and mature pyridinium cross-links and the nonenzymatic cross-link, Pen, and correlated the cross-link content to bone strength.Hcys levels were significantly higher in the Met diet groups than in the normal diet groups. Met-fed rabbits with or without OVX showed a significant reduction of enzymatic cross-links, whereas an increase in Pen was observed in Met-fed rabbits with OVX. The cross-link content of the RLX-treated Met-fed rabbits with OVX was restored to similar levels as the sham group, accompanied by an improvement of bone strength.These results demonstrate that hyperhomocysteinemia reduced bone strength via a reduction of enzymatic cross-links and an increase of nonenzymatic cross-links. RLX may ameliorate hyperhomocysteinemia-induced detrimental cross-linking in rabbits with OVX and may improve bone strength via the amelioration of collagen cross-links.