凝血酶調節素(TM)為細胞膜表面的醣蛋白，高度表現在內皮細胞及其他種類的細胞，如角質形成細胞、成骨細胞及髓系單核球細胞。它最先是被發現具有抗凝血的角色。最近的研究指出它有多重的功能如血管生成、細胞生長及補體活化。TM在單核球/巨噬細胞上和發炎有關，且其表現在生理或病理的情況下會改變。在蝕骨細胞新生作用中，從骨髓或血管系統而來的單核球/巨嗜細胞會互相融合形成多核的細胞，最後參與骨質再吸收。到目前，巨噬細胞上的TM在蝕骨細胞新生作用中的角色尚未被探討。
使用人類周邊血液單核球(PBMCs)及老鼠骨髓得來的巨噬細胞(BMMs)做為前驅細胞。利用髓系專一性TM剃除老鼠及缺乏TM之N端功能區老鼠做為研究模式。使用巨噬細胞生長因子(M-CSF)和核內細胞因子活化型B細胞κ輕鏈促進物之受體活化器(RANKL)誘導蝕骨細胞形成。
結果顯示，TM的表現在蝕骨細胞新生作用中有減低的情形。在髓系專一性TM剃除老鼠中，缺乏TM會增加蝕骨細胞的形成。而在缺乏TM之N端功能區老鼠也有一致的現象，顯示在蝕骨細胞新生作用中，TM之N端功能區扮演一定程度的角色。而在處理RANKL後，髓系專一性剃除TM的老鼠BMMs會產生較多的促發炎因子高動性分群組1(HMGB1)，則暗示TM可能透過干擾HMGB1在蝕骨細胞上的功能來調節蝕骨細胞新生作用。
總結來說，TM的表現和蝕骨細胞的分化過程是負相關的。而由上述結果推測TM可能透過調節與與發炎反應有關的角色參與在蝕骨細胞新生作用中，因而對於骨質代謝疾病提供一個新的方向與應用。

Backgrounds:Thrombomodulin (TM), a glycoprotein on the cell surface, is highly expressed in endothelial cells and other numerous cell types such as keratinocyes, osteoblasts and myeloid mononuclear cells. It is first discovered as an anticoagulant factor, and recent studies demonstrate that it has multi-functions including angiogenesis, cell proliferation and complement activation. TM in monocytes/macrophages is associated with inflammation and the expression level is altered in physiological and pathological conditions. In osteoclastogenesis, monocytes /macrophages obtained from bone marrow or vascular-blood system can differentiate to osteoclasts by cell-cell fusion to form multinucleated cells, which are involved in bone resorption. Until now, the role of TM in macrophages in osteoclastogenesis has not been investigated.
Materials and Methods:Osteoclast precursors were isolated from human peripheral blood mononuclear cells (PBMCs) and mouse bone marrow derived macrophages (BMMs). Myeloid-specific TM-deficent mice (LysMcre/TMflox/flox) and mice lacking lectin-like domain of TM (TMLeD/LeD) were used. The differentiation was induced by macrophage-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand (RANKL).
Results:TM expression was decreased during osteoclastogenesis. Results of osteoclast formation from LyMCreTMflox/flox BMMs showed that TM deficiency caused enhancement of osteoclastogenesis. TMLeD/LeD mice BMMs also had higher activity of osteoclast formation, indicating that TM lectin-like domain plays a role in osteoclastogenesis. Finallly, the proinflammatory cytokine high mobility group box 1 (HMGB1) production in LysMCreTMflox/flox BMMs was much more than TMflox/flox group after RANKL treatment, which suggested that TM regulates osteoclastogenesis by interfering the function of HMGB1 in osteoclasts.
Conclusion:Taken together, we showed that TM expression was inversely correlated with the differentiation of osteoclasts. It was speculated that TM may participate in osteoclastogenesis through modulating inflammatory response and which may provide a novel application on osteometabolic diseases.

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