脱落乳牙牙髓干细胞来源外泌体对大鼠TMJ OA软骨下骨稳态的影响
The effects of SHED-EXO on subchondral bone homeostasis during rat TMJ OA
段宇辰 1何睿 1陈晓华 2何峰 2吴凡 2詹英 2苗辉 2于世宾 2逄键梁1
作者信息
- 1. 100142 北京,安徽医科大学第五临床学院,空军特色医学中心口腔科
- 2. 口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔疾病国际联合研究中心,空军军医大学第三附属医院口腔解剖生理学教研室
- 折叠
摘要
目的:探讨关节腔内注射脱落乳牙牙髓干细胞外泌体(SHED-EXO)对大鼠颞下颌关节骨关节炎(TMJ OA)软骨下骨稳态的影响.方法:36只雄性SD大鼠随机分为3组(n=12):对照组(CON组)、碘乙酸钠(MIA)诱导TMJ OA组(MIA组)和SHED-EXO治疗TMJ OA组(治疗组).治疗2、6周后取材,Micro-CT、荧光双标、TRAP染色、免疫组化染色和免疫荧光染色检测成骨与破骨情况,qRT-PCR检测ADAMTs5,IL-1β,OCN,OPG/RANKL等相关因子表达变化.结果:MIA组骨量丧失明显,骨髓腔明显扩大,相较于CON组,BV/TV和Tb.Th降低(P＜0.001),BS/BV、Tb.Sp和Tb.N升高(P＜0.01),且5 d内骨生成速率低于对照组(P＜0.001);SHED-EXO组与MIA组相比,骨形态与骨量显著增加,BV/TV和Tb.Th升高(P＜0.01),BS/BV、Tb.Sp和Tb.N降低(P＜0.05),骨生成速率增加(P＜0.01).2、6周后,MIA组较对照组与治疗组,下骨内破骨细胞数量均升高(P＜0.01),而H型血管与OCN阳性面积减少(P＜0.01).结论:关节腔注射SHED-EXO 可以通过促进成骨和抑制破骨调节TMJ OA大鼠髁突软骨下骨稳态.
Abstract
Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.
关键词
SHED-EXO/骨稳态/外泌体/骨关节炎/颞下颌关节Key words
SHED-EXO/Bone homeostasis/Exosomes/Osteoarthritis/Tem-poromandibular joint引用本文复制引用
基金项目
国家自然科学基金(81970953)
国家自然科学基金(82271000)
陕西省自然科学基础研究计划重点项目(2022JZ-52)
陕西省重点研发计划(2023-YBSF-459)
出版年
2024
NETL
NSTL
万方数据