摘要
目的研究p38丝裂原活化蛋白激酶(p38MAPK)信号途径在甲状旁腺素相关肽(PTHrP)诱导的破骨细胞生成和骨吸收中的作用。方法取小鼠骨髓细胞,在PTHrP(45ng/ml)的刺激下,在不同试验组中分别入0.1、1.0及10μmol/L的p38MAPK抑制剂Fr167653,继续培养6d。抗酒石酸染色,进行破骨细胞计数。在小鼠颅骨部位注射PTHrP建立骨吸收和高钙血症动物模型。每日给予p38MAPK抑制剂Fr16765330mg/kg,每日2次,X线片观察骨吸收面积,组织学检查计算单位面积内破骨细胞数目,采集血样观察全血内游离钙水平。结果PTHrP刺激下,大量破骨细胞生成(118.9±28.3)个/孔;加入0.1μmol/LFr167653可以部分抑制破骨细胞的生成(79.6±28.0)个/孔,加入10μmol/LFr167653几乎全抑制了破骨细胞生成(7.4±0.4)个/孔,每日给予Fr16765330mg/kg,每日2次,可以明显抑制骨吸收,表现为X线片上骨吸收面积减少,单位面积内破骨细胞数目减少,但是并不能有效地抑制高钙血症。结论抑制p38MAPK信号途径可以抑制破骨细胞的分化和局部骨吸收。
Objective To study the role of p38 mitogen-activated protein kinase （p38 MAPK） pathway in osteoclastogenseis in vitro and bone resorption in vivo. Methods Under the stimulation by parathyroid hormone-rehted peptide （FFHrP） （45 ng/ml）, murine primary bone marrow cell were cultured for 6 days in the presence of 0.1, 1.0 and 10 μmol/L of p38 MAPK inhibitor, Fr167653. After TARP staining, number of osteoclasts was counted. Bone resorptive and hypercalcemia animal model were established by injection of PTHrP on the mice calvarias, p38 MAPK inhibitor Fr167653 was administrated subcutaneously daily. The dose was 30 mg/kg （twice per day）, photographical bone resorption area were evaluated by imaging analysis system and osteoclast number per unite bone area were evaluated histological. Whole blood ionized calcium level were also measured. Results Large number of osteoclasts were formed under the stimulation of PTHrP （118.9±8.3 ） N/well; Osteoclast formation was partially inhibited by 0.1μmol/L of Fr167653 （79.6±28.0） N/well, and almost abrogated by 10μmol/L of Fr167653 （7.4±0.4） N/well. At dose of 30 mg/kg （twice per day）, bone resorption area and osteoclast number per unite bone area were reduced significantly. However, whole blood ionized calcium were kept on the high level as hyperealcemia. Conclusions Inhibition of p38 MAPK pathway is effective to block the osteoclast formation in vitro and bone resorption in vivo, but not hyperealcemia in vivo.
出处
《中华风湿病学杂志》
CAS
CSCD
2006年第4期202-205,i0001,共5页
Chinese Journal of Rheumatology
基金
陕西省科技攻关基金资助项目[2005K14-G2(1)]
