Abstract:
It is well established that inflammatory processes in the vicinity of bone often induce osteoclast formation and bone resorption. Effects of inflammatory processes on bone formation are less studied. Therefore, we investigated the effect of locally induced inflammation on bone formation. Toll-like receptor (TLR) 2 agonists LPS from Porphyromonas gingivalis and PAM2 were injected once subcutaneously above mouse calvarial bones. After five days, both agonists induced bone formation mainly at endocranial surfaces. The injection resulted in progressively increased calvarial thickness during 21 days. Excessive new bone formation was mainly observed separated from bone resorption cavities. Anti-RANKL did not affect the increase of bone formation. Inflammation caused increased bone formation rate due to increased mineralizing surfaces as assessed by dynamic histomorphometry. In areas close to new bone formation, an abundance of proliferating cells was observed as well as cells robustly stained for Runx2 and alkaline phosphatase. PAM2 increased the mRNA expression of Lrp5, Lrp6 and Wnt7b, and decreased the expression of Sost and Dkk1. In situ hybridization demonstrated decreased Sost mRNA expression in osteocytes present in old bone. An abundance of cells expressed Wnt7b in Runx2-positive osteoblasts and ß-catenin in areas with new bone formation. These data demonstrate that inflammation, not only induces osteoclastogenesis, but also locally activates canonical WNT signaling and stimulates new bone formation independent on bone resorption.
摘要:
众所周知,骨附近的炎症过程通常诱导破骨细胞形成和骨吸收。炎症过程对骨形成的影响研究较少。因此,我们研究了局部诱导的炎症对骨形成的影响。将来自牙龈卟啉单胞菌的Toll样受体(TLR)2激动剂LPS和PAM2皮下注射一次到小鼠颅骨上方。五天后,两种激动剂主要在颅骨表面诱导骨形成。注射导致21天内颅骨厚度逐渐增加。观察到过量的新骨形成主要与骨吸收腔分离。抗RANKL不影响骨形成的增加。通过动态组织形态计量学评估,由于矿化表面增加,炎症导致骨形成速率增加。在接近新骨形成的区域,观察到大量的增殖细胞以及对Runx2和碱性磷酸酶进行强染色的细胞。PAM2增加了Lrp5、Lrp6和Wnt7b的mRNA表达,并降低了Sost和Dkk1的表达。原位杂交表明旧骨中存在的骨细胞中SostmRNA表达降低。大量细胞在Runx2阳性成骨细胞中表达Wnt7b,并在具有新骨形成的区域中表达β-catenin。这些数据表明炎症,不仅诱导破骨细胞生成,但也局部激活典型的WNT信号和刺激新骨形成独立于骨吸收。