ＴＭＤ１蛋白用於治療骨質流失疾病

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

106103272

專利證號

I 650135

專利獲證名稱

ＴＭＤ１蛋白用於治療骨質流失疾病

專利所屬機關 (申請機關)

高雄醫學大學

獲證日期

2019/02/11

技術說明

研究證實，過多的發炎反應將促使蝕骨細胞(osteoclasts)的形成，進而導致骨質的流失或骨密度的下降，最終造成疾病，例如：骨質疏鬆症(osteoporosis)。Receptor activator of nuclear factor-κB ligand (RANKL)是誘導骨髓前驅細胞(bone marrow-derived macrophages, BMM) 分化形成蝕骨細胞與骨溶蝕活性的重要因子。RANKL的作用機制是促使骨髓前驅細胞分泌high mobility group box-1 (HMGB1)到細胞膜外，再藉由HMGB1與前驅細胞膜上的receptor for advanced glycation endproducts (RAGE)結合進而完成蝕骨細胞的分化與活性。另有文獻證實，凝血酶調節素的類凝集素功能區(thrombomodulin lectin-like domain, TMD1)具有干擾HMGB1-RAGE交互作用，而達到抑制發炎的效果。本研究中利用細胞與動物模式研究發現，我們證實TMD1能夠有效抑制RANKL誘導的蝕骨細胞形成與其骨溶蝕活性，且此效用呈現劑量相關性。故我們認為TMD1應該是一種可用於治療骨質流失疾病的新穎蛋白質藥物。 Growing evidences indicated that excessive inflammation promotes the formation of osteoclasts, and then causes the bone loss and related disorders. Receptor activator of nuclear factor-κB ligand (RANKL) is a critical factor to induce the differentiation of osteoclasts from bone marrow-derived macrophages (BMM). The mechanism of RANKL is promotes the production of extracellular high mobility group box-1 (HMGB1) of BMM, and which activate the receptor for advanced glycation endproducts (RAGE) on the cell surface, finally to differentiate osteoclasts. Moreover, thrombomodulin lectin-like domain (TMD1) has been demonstrated that can inhibit the inflammation by interfere the interaction of HMGB1 and RAGE. Using the in vitro and in vivo models, we showed that TMD1 significantly attenuates the osteoclast differentiation and bone resorption in a dose-dependent manner. Thus, we indicate that TMD1 may be a new therapeutic treatment for bone loss diseases.

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