FGF23、MEPE和sFRP4在肿瘤性骨软化症发病机制中的作用

Role of fibroblast growth factor 23,matrix extracellular phosphoglycoprotein and secreted frizzled related protein 4 in pathogenesis of tumor induced osteomalacia

目的探讨成纤维细胞生长因子-23（FGF-23）、细胞外基质磷酸糖蛋白（MEPE）和分泌型卷曲相关蛋白（sFRP4）在肿瘤性骨软化症（TIO）发病机制中的作用。方法TIO肿瘤8例（T1-T8），其他间叶肿瘤5例（C1-C5），低血磷骨软化症病人行股骨手术，病理为凝血坏死组织1例（P1），正常人骨骼、肌肉组织各2例（B1、B2、M1和M2）。RT-PCR检测组织中FGF23、MEPE、sFRP4 mRNA的表达，Western blot检测TIO肿瘤FGF23蛋白的表达。TIO 4例（T1、T3、T4和T7）及P1在手术前后分别取血测定血清磷和FGF23（ELISA）水平。结果TIO肿瘤有数量不等的FGF23和MEPE的mRNA表达，部分肿瘤表达sFRP4的mRNA。7／8例TIO肿瘤有不同强度FGF23蛋白表达。TIO术前血FGF23升高，术后2～24h降至正常；血磷3-10d缓慢升至正常，P1病人术后血FGF23无变化，血磷未上升。FGF23与MEPE mRNA正相关（r=0．884，P〈0．05），FGF23 mRNA与蛋白表达之间成正相关关系（r=0．921，P〈0．05）。结论FGF23是TIO发病的主要原因，MEPE在TIO肿瘤发病中起到一定作用，sFRP4的作用尚不明确。

Objective To evaluate the role of Fibroblast growth factor 23 （ FGF-23 ）, matrix extracellular phosphoglycoprotein （MEPE） and secreted Frizzled related protein 4 （sFRP4） in the pathogenesis of tumor induced osteomalacia （TIO）. Methods The mRNA expressions of FGF23, MEPE and sFRP4 were detected in 8 TIO tumors （T1-T8）, 5 other mesenchymal tumors（C1-C5）, 2 normal bone tissues（B1-B2）, 2 normal muscle tissues（M1- M2）, blood clotting and necrostic tissue of bone in a patient of hypophospatemic osteomalacia but not TIO （ P1 ） using RT-PCR. The FGF23 protein expressions were analyzed in 8 TIO tumors using Western blot. Serum FGF23 （ELISA） and phosphate were measured before and after operation in 4 TIO （T1,3,4,7） and P1 patients. Results The mRNA of FGF 2 3 and MEPE were expressed in TIO tumors abundantly . Some TIO tumors expressed sRP 4 mRNA. 7/8 TIO tumors expressed various FGF23 proteins. Serum FGF23 of TIO patients was increased, and decreased after tumor resections in 2 - 24 hrs. The increase of serum phosphate was slower than FGF23 degression （ in 3 - 10 days）. Serum FGF23 was stably high in P1 patient without serum phosphate elevation. The expressions of FGF23 and MEPE mRNA were related （ r = 0. 884, P 〈 0. 05 ）. There was a positive relationship between FGF23 mRNA and protein expression （ r = 0. 921, P 〈 0. 05 ）. Conclusion FGF23 plays an important role in the pathogenesis of TIO. MEPE may be involved in the pathogenesis of TIO. The role of sFRP4 in pathogenesis of TIO is still need to be explored.