颅骨锁骨发育不全（CCD）是RUNX2突变引起的单基因显性遗传病，表现为全身多发性骨骼和牙齿异常。RUNX2突变通过干扰牙槽骨改建影响恒牙萌出。前期发现：CCD患者牙槽骨中破骨细胞减少，骨密度增加；转录组测序筛出一个新的破骨分化特异性的长链非编码RNA（LncRNA-ROD）差异表达；RUNX2突变和LncRNA-ROD均可通过Akt通路调控破骨分化；LncRNA-ROD可与hnRNPA1蛋白结合。由此，提出科学假设：RUNX2突变通过LncRNA-ROD/hnRNPA1/Akt通路调控破骨分化。本课题拟研究：（1）RUNX2突变对破骨分化的调控作用；（2）RUNX2突变通过LncRNA-ROD调控破骨分化的机制；（3）LncRNA-ROD招募hnRNPA1调控CALM表达，参与Akt通路激活，进而调控破骨分化的机制。本研究有助于揭示CCD恒牙阻生的机制，为牙齿萌出和骨改建的研究提供基础。

Cleidocranial dysplasia (CCD) is an autosomal dominant genetic disease caused by RUNX2 mutation. The main clinical manifestation includes multiple skeletal disorders and dental anomalies. Our previous studies found that, the bone density of the alveolar bone around impacted was increased and osteoclasts differentiation was restricted in CCD patients. We found a novel and osteoclast specific long noncoding RNA (LncRNA-ROD) was down-regulated by mutant RUNX2. Mutant RUNX2 and LncRNA-ROD both exert regulation effect of osteoclasts differentiation through Akt pathway. hnRNPA1 act as the potential binding protein of LncRNA-ROD. Therefore, we hypothesize that mutant RUNX2 may regulate osteoclasts differentiation through LncRNA-ROD/hnRNPA1/Akt pathway. And we will focus our research to the following aspects: (1) The direct effect of RUNX2 mutation on osteoclasts differentiation. (2) The impact of RUNX2 mutation on osteoclasts differentiation through LncRNA-ROD. (3) The molecular mechanism of LncRNA-ROD on osteoclasts differentiation by recruiting hnRNPA1 to CALM which may activate Akt pathway. This study will somehow explain the mechanism of impacted permanent teeth in CCD patients, and make foundation for the exploration of tooth eruption and bone remodeling.