外泌体miR-338对骨质疏松大鼠骨代谢水平、骨小梁微结构和骨生物力学的影响

摘要 目的：探讨外泌体miR-338对骨质疏松大鼠骨代谢水平、骨小梁微结构和骨生物力的影响。方法：采用健康成年SPF级SD雄性大鼠进行骨髓间充质干细胞（BMSCs）分离。采用双侧卵巢摘除手术方法构建了骨质疏松大鼠模型。采用qRT-PCR法检测miR-338的表达水平；检测大鼠的骨密度，骨小梁微结构和骨生物力学指标。结果：与空白对照组相比，OP模型组、OP+ ExoBMSCs、抑制组和过表达组miR-338的表达水平明显更高（P＜0.05）；抑制组的miR-338的表达水平低于OP模型组、OP+ExoBMSCs和过表达组（P＜0.05）；与空白对照组相比，OP模型组、OP+ ExoBMSCs、抑制组和过表达组OC、PINP、BALP的表达水平明显更低（P＜0.05）；抑制组的OC、PINP、BALP的表达水平明显高于OP模型组、OP+ ExoBMSCs和过表达组（P＜0.05）；与空白对照组相比，OP模型组、OP+ ExoBMSCs、抑制组和过表达组BV/TV、Th.N、Tb.Th、Conn.D水平更低，而Tb.Sp、SMI明显更高（P＜0.05）；抑制组组的BV/TV、Th.N、Tb.Th、Conn.D水平明显高于OP模型组、OP+ ExoBMSCs和过表达组，而Tb.Sp、SMI更低（P＜0.05）；与空白对照组相比，OP模型组、OP+ ExoBMSCs、抑制组和过表达组BMD、最大荷载、最大应力、最大位移、刚度水平更低（P＜0.05）；抑制组的BMD、最大荷载、最大应力、最大位移、刚度水平高于OP模型组、OP+ExoBMSCs和过表达组（P＜0.05）。结论：BMSCs源性的miR-338可影响骨质疏松大鼠骨代谢、骨小梁微结构和骨生物力学状态。

Effects of Exosome MiR-338 on Bone Metabolism, Trabecular Microstructure and Bone Biomechanics in Osteoporotic Rats

ABSTRACT Objective: To investigate the effects of exosome miR-338 on bone metabolism, trabecular microstructure and bone biodynamics in osteoporosis rats. Methods: Bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy adult SPF SD male rats. A rat model of osteoporosis was established by bilateral ovariectomy. The expression level of miR-338 was detected by qRT-PCR. Bone mineral density, trabecular microstructure and bone biomechanics were measured. Results: Compared with blank control group, the expression level of miR-338 was higher in OP model group, OP+ ExoBMSCs, inhibition group and overexpression group (P<0.05). The expression level of miR-338 in inhibition group was lower than that in OP model group, OP+ ExoBMSCs and overexpression group (P<0.05). Compared with blank control group, the expression levels of OC, PINP and BALP in OP model group, OP+ ExoBMSCs, inhibition group and overexpression group were lower (P<0.05). The expression levels of OC, PINP and BALP in inhibition group were higher than those in OP model group, OP+ ExoBMSCs and overexpression group (P<0.05). Compared with blank control group, the levels of BV/TV, Th.N, Tb.Th and Conn. D in OP model group, OP+ ExoBMSCs, inhibition group and overexpression group were lower, Tb.Sp and SMI were higher (P<0.05). The levels of BV/TV, Th.N, Tb.Th and Conn.D in inhibition group were higher than those in OP model group, OP+ ExoBMSCs and overexpression group (P<0.05), Tb.Sp and SMI were lower (P<0.05). Compared with blank control group, the levels of BMD, maximum load, maximum stress, maximum displacement and stiffness in OP model group, OP+ ExoBMSCs, inhibition group and overexpression group were lower (P<0.05). The levels of BMD, maximum load, maximum stress, maximum displacement and stiffness in inhibition group were higher than those in OP model group, OP+ ExoBMSCs and overexpression group (P<0.05). Conclusion: BMScS-derived miR-338 can affect bone metabolism, trabecular microstructure and bone biomechanical status in osteoporosis rats.