背景:下颌髁突发育不全会对患者的面部外观和颌面功能产生负面影响。
目的:研究局部注射药物阿巴罗帕拉肽(ABL)的效果,甲状旁腺激素相关蛋白(PTHrP)的类似物,关于促进下颌髁突延长的研究。
方法:30只青春期雄性Sprague-Dawley大鼠随机分为两组,每3天在颞下颌关节(TMJ)腔内注射ABL或生理盐水(对照)。在注射后2、4和6周进行锥形束计算机断层扫描和免疫组织化学测定。用ABL或PBS处理下颌髁突软骨细胞(MCC)和前成骨细胞,接着是CCK-8检测,IC50,实时PCR检测,Westernblot和免疫荧光染色。
结果:体内,与对照组相比,ABL组下颌髁突长度显著增加(6周时增加1.34±0.59mm),软骨层的厚度,并增强了基质合成。ABL组SOX9、COLⅡ、PTHrP和PTH1R,软骨中COXX的下调,RUNX2的上调和软骨下骨中破骨细胞生成不变。体外,TMJ内注射ABL促进MCC增殖,随着软骨形成基因的表达上调,并增强前成骨细胞的成骨分化。
结论:颞下颌关节腔内注射阿巴罗帕肽可促进青春期大鼠下颌髁突软骨的软骨形成和软骨下骨的骨化,从而促进下颌髁突的延长。
BACKGROUND: Mandibular condylar hypoplasia negatively affects patient\'s facial appearance and dentofacial function.
OBJECTIVE: To investigate the effect of local injection of the drug abaloparatide (ABL), an analogue of parathyroid hormone related protein (PTHrP), on promoting lengthening of the mandibular condyle.
METHODS: Thirty adolescent male Sprague-Dawley rats were randomly divided into two groups, which received the injection of ABL or normal saline (the control) every 3 days in the temporomandibular joint (TMJ) cavity. Cone-beam computed tomography and immunohistochemistry assays were performed at 2, 4 and 6 weeks since the injection. Mandibular condylar chondrocytes (MCC) and pre-osteoblasts were treated with ABL or PBS, followed by the CCK-8 detection, IC50, real-time PCR assay, Western Blot and immunofluorescence staining.
RESULTS: In vivo, compared with the control, the ABL group significantly increased the mandibular condylar process length (by 1.34 ± 0.59 mm at 6 weeks), the thickness of the cartilage layer, and enhanced the matrix synthesis. The ABL group had significant up-regulation of SOX 9, COL II, PTHrP and PTH1R, down-regulation of COL X in the cartilage, up-regulation of RUNX 2, and unchanged osteoclastogenesis in the subchondral bone. In vitro, the intra-TMJ injection of ABL promoted the MCC proliferation, with up-regulated expression of chondrogenic genes, and enhanced osteogenic differentiation of the pre-osteoblasts.
CONCLUSIONS: Intra-TMJ injection of abaloparatide promotes mandibular condyle lengthening in the adolescent rats via enhancing chondrogenesis in the mandibular condylar cartilage and ossification in the subchondral bone.