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

作　　者：段宇辰 何睿 陈晓华 何峰 吴凡 詹英 苗辉 于世宾 逄键梁 DUAN Yuchen;HE Rui;CHEN Xiaohua;HE Feng;WU Fan;ZHAN Ying;MIAO Hui;YU Shibin;PANG jianliang(the Fifth Clinical Medical College of Anhui Medical University,Department of Stomatology,Air Force Medical Center,PLA,China,100142 Beijing;State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi International Joint Research Center for Oral Diseases,Department of Oral Anatomy and Physiology and TMD,The Third Hospital Affiliated of Air Force Military Medical University,China)

机构地区：[1]安徽医科大学第五临床学院,空军特色医学中心口腔科,北京100142 [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

出　　处：《实用口腔医学杂志》2024年第3期315-322,共8页Journal of Practical Stomatology

基　　金：国家自然科学基金(编号:81970953,82271000);陕西省自然科学基础研究计划重点项目(编号:2022JZ-52);陕西省重点研发计划(编号:2023-YBSF-459)。

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。Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from human 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.Additio nally,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 lo wer(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 lower than that of the control group(P<0.001).When compared to th e MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were inc reased(P<0.01),w hile 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 regulate 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 

分 类 号：R782.6[医药卫生—口腔医学]