Abstract:【Objective】To investigate the mechanism of long non-coding RNA insulin-like growth factor 2 antisense transcript (lncRNA IGF2-AS) in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). 【Methods】 Fifty 6-month-old SD female rats were selected as the research objects and divided into 5 groups with 10 rats in each group by random number table method. Group A was sham operation group, group B, group C and group D underwent surgical resection of both ovaries to construct the ovariectomized (OVX) rat model (the success rate of each group was 100%), and the remaining 10 were control group after successful construction. After the OVX rat model was successfully constructed, the rats in group C were given lncRNA IGF2-AS simulants, the rats in group D were given lncRNA IGF2-AS inhibitors, and the other groups were given equal volume normal saline. The rats in all groups were routinely fed for 8 weeks. Bone mineral density, body weight, blood urea nitrogen level, femur biomechanical strength, serum index level, lncRNA IGF2-AS, miR-3126-5p and KLK4 expression levels, and BMSCs osteogenic differentiation level were compared in all groups after feeding for 8 weeks. 【Results】 There was no significant difference in body weight among all groups (P>0.05). The bone mineral density of L5 and femur of rats in groups B and D were lower than those in group A and the control group, the bone mineral density of L5 and femur of rats in group C was higher than that in group A and the control group, and the bone mineral density of L5 and femur of rats in group B was higher than that in group D, with statistical significance (P<0.05). The blood urea nitrogen levels of rats in group B, C and D were higher than those in group A and the control group, the blood urea nitrogen level of rats in group C was lower than that in group B and D, and the blood urea nitrogen level of rats in group B was lower than that in group D, all difference were statistical significance (P<0.05). The maximum femur load and Young's modulus of rats in group B, C and D were lower than those in group A and the control group, and the maximum femur load and Young's modulus of rats in group C were higher than those in group B and D, and those in group B were higher than those in group D, with all statistical significance (P<0.05). Serum Ca and P levels of rats in group B, C and D were lower than those in group A and the control group, while serum ALP, PⅠNP and CTX-Ⅰ levels were higher than those in group A and control group, the difference were significant (P<0.05). The serum Ca and P levels of rats in group C were higher than those in group B and D, and levels of Ca and P in group B was higher than those in group D; While serum ALP, PⅠNP and CTX-Ⅰ levels of rats in group C were lower than those in group B and D, and those in group B were lower than those in group D. All differences were statistically significant (P<0.05). There was no significant difference in the expression levels of lncRNA IGF2-AS, miR-3126-5p and KLK4 in group A, group B and the control group (P>0.05). The expression levels of lncRNA IGF2-AS, miR-3126-5p and KLK4 in group C were higher than those in groups A, B, D and control group, and the differences were statistically significant (P<0.05). There was no statistically significant difference in the distribution of BMSCs osteoblasts between group A and control group. The distribution of BMSCs osteoblasts in groups B, C and D was less than that in groups A and control group, and the distribution of BMSCs osteoblasts in group C was more than that in groups B and D, and group B has more distribution of BMSCs osteoblasts than that in group D. 【Conclusion】 Overexpression of lncRNA IGF2-AS can promote osteogenic differentiation of BMSCs by regulating miR-3126-5p/KLK4 signaling pathway, improve bone mineral density, blood urea nitrogen levels and serum levels of Ca, P, ALP, PⅠNP and CTX-Ⅰ, and enhance the biomechanical strength of femur.
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