Effect of Human Wnt10b Transgene Overexpression on Peri-Implant Osteogenesis in Ovariectomized Rats (Retracted article. See vol. 33, pg. 572, 2022)
Effect of Human Wnt10b Transgene Overexpression on Peri-Implant Osteogenesis in Ovariectomized Rats (Retracted article. See vol. 33, pg. 572, 2022)
复制标题
DOI：
10.1089/hum.2017.256
复制
发表时间：
2018-12-01
影响因子：
4.2
通讯作者：
Hou, Wenjie
中科院分区：
文献类型：
--
作者：
Chi, Chi;Mao, Min;Hou, Wenjie
本研究旨在探讨人Wnt10b （hWnt10b）基因在去卵巢（OVX）大鼠体内的表达对促进钛植入物周围骨整合的作用，为植入物治疗骨质疏松提供新的策略。通过切除双侧卵巢建立大鼠体内骨质疏松模型，观察Wnt通路相关基因的表达变化。在有股骨缺损的OVX大鼠中，通过腺病毒载体表达的hWnt10b在植入之前被局部递送到缺损部位。植入后1周和3周采集股骨周围组织进行影像学、生物力学测试、分子和组织学分析。在体外模型中，转染含有hWnt10b （Ad-hWnt10b）的腺病毒的骨髓基质细胞（BMSCs）在成脂培养基中培养2周，然后在成骨诱导培养基中培养2周。采用茜素红染色、油红O染色、逆转录聚合酶链反应和Western blot分析hWnt10b表达对BMSC分化的影响。OVX大鼠Wnt通路基因表达明显下调。在诱导股骨缺损之前，用Ad-hWnt10b处理OVX大鼠显示ALP、Runx-2和骨钙素表达显著增加，组织蛋白酶K表达显著降低。组织学和影像学分析显示，与未治疗的对照组相比，Ad-hWnt10b组骨钙素阳性细胞的数量和种植体周围新形成骨的密度增加。同时，Ad-hWnt10b-BMSCs的成骨能力显著增强，脂肪生成能力显著降低。在OVX条件下，hWnt10b可能加速种植体周围的骨整合，随后增强骨再生和种植体稳定。
This study aimed to investigate the efficacy of human Wnt10b (hWnt10b) transgene expression in ovariectomized (OVX) rats to accelerate osseointegration around titanium implants, and to provide a new strategy for treating osteoporosis with implants. An in vivo osteoporosis model was generated via bilateral ovariectomy in rats, and changes in expression of Wnt pathway-related genes were investigated. In OVX rats with a femur defect, hWnt10b expressed from an adenovirus vector was locally delivered to the defect site prior to implant placement. Surrounding femur tissues were collected 1 and 3 weeks after implantation for imaging, biomechanical testing, and molecular and histological analyses. In an in vitro model, bone-marrow stromal cells (BMSCs) transfected with adenovirus containing hWnt10b (Ad-hWnt10b) were cultured for 2 weeks in adipogenic medium followed by 2 weeks in osteogenic induction medium. Alizarin Red staining and Oil Red O staining, as well as reverse transcription polymerase chain reaction and Western blot analyses, were performed to assess the effect of hWnt10b expression on BMSC differentiation. Expression of Wnt pathway genes was significantly downregulated in OVX rats. OVX rats treated with Ad-hWnt10b prior to induction of a femur defect showed markedly increased ALP, Runx-2, and osteocalcin expression and decreased cathepsin K expression. Histological and imaging analysis showed increases in the number of osteocalcin-positive cells and the density of newly formed bone surrounding the implant in the Ad-hWnt10b group relative to the untreated control. Meanwhile, Ad-hWnt10b-BMSCs showed significantly increased osteogenesis and decreased adipogenesis. hWnt10b may accelerate osseointegration around implants and subsequently enhance bone regeneration and implant stabilization under OVX conditions.