Mulberry-Derived Oligonucleotides Significantly Improved Osteoporosis in Mice
The objective of this experiment was to explore the improvement effects of ASON-OP,an oligonu-cleotide derived from the mulberry.Thirty female mice were randomly divided into five groups:sham surgery group,model control group,positive control group,ASON-OP group,and ASON-NC group(ASON-NC is a nonsense sequence,as negative control),with six mice in each group.Except for the mice in the sham surgery group,bilateral ovariectomy(OVX)was performed on mice in the other four groups to induce the osteoporo-sis mouse model.After successful modeling,continued to feed for 1 week,and then administered the drug.Mice in the sham surgery group and model control group were given 300 μL normal saline per day by gavage;mice in the positive control group were injected subcutaneously with teriparatide at the dose of 80 μg/(kg BW·d),five times a week;mice in the ASON-NC group were given ASON-NC solution by ga-vage,2 mg/(kg BW·d);mice in the ASON-OP group were given ASON-OP solution by gavage,2 mg/(kg BW·d).The mice were continuously administered for 4 weeks,and their bone tissue microstruc-ture and bone turnover markers were measured.The results showed as follows:compared to the model control group and ASON-NC group,mice gavaged with oligonucleotide ASON-OP for 4 weeks significantly increased the bone mineral density of OVX mice(P<0.05);it significantly increased the serum content of osteocalcin(OCN)as a bone formation marker of OVX mice(P<0.05),and significantly decreased the serum content of type Ⅰ collagen C-terminal telopeptide(CTX-1)as a bone resorption marker(P<0.05);it also significantly increased the mRNA relative expression levels of the bone formation-related genes Runt-related transcription factor 2(Runx2),alkaline phosphatase,liver/bone/kidney(Alpl)and bone gamma-carboxyglutamate protein(Bglap)in the femur of OVX mice(P<0.05).In conclusion,ASON-OP,an oligonucleotide derived from mulberry,exhibits significant anti-osteoporotic effect.[Chinese Journal of Animal Nutrition,2024,36(1):602-609]