Effect of alendronate on endochondral ossification in mandibular condyles of growing rats.
Effect of alendronate on endochondral ossification in mandibular condyles of growing rats.
复制标题
DOI：
10.4081/ejh.2012.24
复制
发表时间：
2012-05-25
期刊：
影响因子：
--
通讯作者：
Arana-Chavez VE
中科院分区：
文献类型：
--
作者：
Bradaschia-Correa V;Barrence FA;Ferreira LB;Massa LF;Arana-Chavez VE
在髁突软骨内骨化过程中，骨组织对钙化软骨的替代依赖于骨细胞的再吸收活性。部分吸收后，钙化的软骨间隔被成骨细胞分泌的初级骨基质覆盖。骨粘附素（Osteoadherin，OSAD）是一种存在于骨基质中的小分子蛋白多糖，在软骨内骨化过程中不存在于软骨中。本研究的目的是分析阿仑膦酸钠，一种已知的药物，抑制破骨细胞的骨吸收，对年轻大鼠下颌骨髁突的软骨内骨化的影响，通过评估破骨细胞的分布和骨基质沉积中的OSAD的存在。Wistar新生大鼠（n=45）从出生之日起每天注射阿仑膦酸钠（n=27）或无菌生理盐水作为对照（n=18），直至4、14和30日龄。在上述日期，下颌骨髁状突收集和处理的透射电子显微镜分析。标本还提交了抗酒石酸酸性磷酸酶（TRAP）组织化学和免疫电镜检测OSAD。阿仑膦酸钠治疗并不妨碍髁突生长过程中骨化区破骨细胞的募集和融合，但它们呈现失活表型。骨化区的骨小梁由软骨基质组成，覆盖着一层原发性骨基质，在所有研究时间点对OSAD呈免疫阳性。显然，阿仑膦酸钠阻碍了下颌升支钙化软骨的去除和骨小梁的成熟，而在对照组中，它们正常发生。这些发现强调了给予关注的潜在副作用的双膦酸盐给年轻患者一旦它可能代表一个风险，扰乱颌面部的发展。
The replacement of the calcified cartilage by bone tissue during the endochondral ossification of the mandibular condyle is dependent of the resorbing activity of osteoclats. After partial resorption, calcified cartilage septa are covered by a primary bone matrix secreted by osteoblasts. Osteoadherin (OSAD) is a small proteoglycan present in bone matrix but absent in cartilage during the endochondral ossification. The aim of this study was to analyze the effect of alendronate, a drug known to inhibit bone resorption by osteoclasts, on the endochondral ossification of the mandibular condyle of young rats, by evaluating the distribution of osteoclasts and the presence of OSAD in the bone matrix deposited. Wistar newborn rats (n=45) received daily injections of alendronate (n=27) or sterile saline solution as control (n=18) from the day of birth until the ages of 4, 14 and 30 days. At the days mentioned, the mandibular condyles were collected and processed for transmission electron microscopy analysis. Specimens were also submitted to tartrate resistant acid phosphatase (TRAP) histochemistry and ultrastructural immunodetection of OSAD. Alendronate treatment did not impede the recruitment and fusion of osteoclasts at the ossification zone during condyle growth, but they presented inactivated phenotype. The trabeculae at the ossification area consisted of cartilage matrix covered by a layer of primary bone matrix that was immunopositive to OSAD at all time points studied. Apparently, alendronate impeded the removal of calcified cartilage and maturation of bone trabeculae in the mandibular ramus, while in controls they occurred normally. These findings highlight for giving attention to the potential side-effects of bisphosphonates administered to young patients once it may represent a risk of disturbing maxillofacial development.