4D label-free quantitative proteomics analysis to screen potential drug targets of Jiangu Granules treatment for postmenopausal osteoporotic rats

Haiming Lin; Wei Zhang; Yashi Xu; Zexing You; Minlin Zheng; Zhentao Liu; Chaoxiong Li

doi:10.3389/fphar.2022.1052922

4D label-free quantitative proteomics analysis to screen potential drug targets of Jiangu Granules treatment for postmenopausal osteoporotic rats

Front Pharmacol. 2022 Nov 1:13:1052922. doi: 10.3389/fphar.2022.1052922. eCollection 2022.

Authors

Haiming Lin¹, Wei Zhang¹, Yashi Xu², Zexing You², Minlin Zheng¹, Zhentao Liu¹, Chaoxiong Li^{3

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Affiliations

¹ College of Integrated Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
² College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
³ Department of Orthopedics, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, China.
⁴ The Third Clinical Medical College, Fujian Medical University, Fuzhou, China.
⁵ Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopaedic Trauma (2020Y2014), Fuzhou, China.

Abstract

Background: Postmenopausal osteoporosis (PMOP) is a disease with a high prevalence in postmenopausal women and is characterized by an imbalance in bone metabolism, reduced bone mass, and increased risk of fracture due to estrogen deficiency. Jiangu granules (JG) is a compound prescription used in traditional Chinese medicine to treat PMOP. However, its definitive mechanism in PMOP is unclear. This study used a 4D label-free quantitative proteomics method to explore the potential therapeutic mechanism of JG in an ovariectomy (OVX) rats' model. Materials and methods: A rat model of PMOP was established by removing the ovaries bilaterally. Nine 3-month-old specific-pathogen-free female SD rats. The nine rats were randomly divided into 3 groups (n = 3 in each group): the sham-operated group (J), the ovariectomy group (NC), and the JG treatment (ZY) group. Proteins extracted from the bone tissue of the lumbar spine (L3, L4) of three groups of rats were analyzed by 4D label-free quantitative proteomics, and proteins differentially expressed after JG treatment and proteins differentially expressed after de-ovulation were intersected to identify proteins associated with the mechanism of PMOP by JG treatment. Result: There were 104 up-regulated and 153 down-regulated differentially expressed proteins (DEPs) in the J group vs. NC group, 107 up-regulated and 113 down-regulated DEPs in the J group vs. ZY group, and 15 up-regulated and 32 down-regulated DEPs in the NC group vs. ZY group. Six potential target proteins for JG regulation of osteoblast differentiation in OVX rats were identified by taking intersections of differential proteins in the J group vs. NC group and NC group vs. ZY group. Conclusion: JG may exert therapeutic effects by modulating the expression levels of target proteins associated with osteoblast differentiation to enhance osteoblast differentiation in OVX rats. These results further uncovered the target proteins and specific mechanisms of JG in treating PMOP, providing an experimental basis for the clinical application of JG in treating PMOP.

Keywords: 4D label-free quantitative proteomics; Jiangu granules; OVX rats; osteoblast differentiation; postmenopausal osteoporotic.