Effect and mechanism of Eucommia ulmoides in regulating the JAK2/STAT3 Signaling pathway in ovariectomized osteoporotic rats
HE Zhi-jun,LIU Feng,LIANG Gui-fang
Guangzhou Panyu District Traditional Chinese Medicine Hospital, Guangzhou510000,China
Abstract:
Objective:?To investigate the protective effects and mechanisms of Eucommia ulmoides on bone in ovariectomized(OVX) rats. Methods:?Forty SD rats were randomly divided into four groups: sham group, OVX group, OVX+Eucommia group, and OVX+estrogen group, with ten rats in each group. The sham group underwent partial removal of the fat tissue adjacent to the ovaries, while the other three groups underwent bilateral ovariectomy to establish the OVX model. The OVX+Eucommia group received a gavage of Eucommia granules at a dosage of 2.76 g/kg, and the OVX+estrogen group was administered ethynyl estradiol at 10 μg/kg via gavage. The sham and OVX groups were given an equivalent volume of distilled water. Micro-computed tomography (Micro CT) was used to assess the microstructural parameters of the femoral trabecular bone in each group, including bone mineral density (BMD), bone mineral content (BMC), trabecular volume fraction (BV/TV), trabecular thickness (Tb.Th), bone surface-to-volume ratio (BS/BV), and trabecular separation (Tb.Sp). A small animal densitometer and bone strength testing apparatus were used to evaluate the bone properties of the femur. Western blot analysis was conducted to measure the levels of JAK2/STAT3 pathway proteins, and enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum levels of bone markers: bone alkaline phosphatase(BALP),procollagen type I N-terminal propeptide (PINP), osteocalcin (OCN), and collagen type I C-terminal cross-linked telopeptide (CTX-1).Results: The OVX rats exhibited significant reductions in BMD, BMC, BV/TV, and Tb.Th, alongside significant increases in BS/BV and Tb.Sp (P<0.01). Eucommia ulmoides significantly improved BMD, BMC, BV/TV, and Tb.Th, and markedly reduced BS/BV and Tb.Sp (P<0.01), while also enhancing bone density and strength. Furthermore, Eucommia ulmoides downregulated serum levels of BALP and CTX-1, while upregulating levels of PINP and OCN in OVX rats (P<0.01). Additionally, mechanistic investigations revealed that Eucommia ulmoides modulated the JAK2/STAT3 signaling pathway in the femur of OVX rats, leading to decreased relative expression levels of p-JAK2 and p-STAT3 (P<0.01). Conclusion:?Eucommia ulmoides can increase femoral bone quality and reduce the severity of osteoporosis in OVX rats, possibly through the modulation of the JAK2/STAT3 signaling pathway
