Use of inhibitor of transcription factor c / EBPβ in preparing medicament for treating postmenopausal osteoporosis

Abstract

Provided is use of an inhibitor of transcription factor C / EBPβ in preparing a medicament for treating postmenopausal osteoporosis (PMOP). Specifically, provided is use of compound # 11a and CF3CN in preparing a medicament for treating PMOP. The C / EBPβ-AEP pathway is involved in promoting the synthesis of FSHβ in menopausal models. By reducing the transcription factor activity of C / EBPβ, the expression of FSH in the pituitary can be reduced, thereby promoting osteogenic differentiation, inhibiting osteoclastic resorption, and effectively alleviating the symptoms of PMOP. Compounds # 11a and CF3CN can effectively achieve the dual functions of anti-bone resorption and osteogenesis promotion, thereby achieving a coupled therapeutic effect for PMOP.

Description

Application of inhibitors of transcription factor C / EBPβ in the preparation of drugs for treating postmenopausal osteoporosis Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to the application of inhibitors of transcription factor C / EBPβ in the preparation of drugs for treating postmenopausal osteoporosis. Background Technology

[0002] Osteoporosis is a systemic orthopedic disease characterized by bone loss and disruption of normal bone structure, leading to increased susceptibility to fractures. Maintaining bone homeostasis depends on a dynamic balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation; imbalance results in osteoporosis, multiple myeloma, osteosclerosis, and other orthopedic diseases. According to the World Health Organization, approximately 2 billion people worldwide suffer from osteoporosis, with a high prevalence in postmenopausal women. Therefore, research into the pathogenesis and potential therapeutic targets of postmenopausal osteoporosis (PMOP) is of great significance. Recent studies have shown that the rise in follicle-stimulating hormone (FSH) levels secreted by pituitary cells after menopause is a significant contributing factor to PMOP. Therefore, inhibiting the increase in postmenopausal FSH levels has important theoretical implications and broad clinical value.

[0003] Medications for treating osteoporosis can be categorized into anti-resorption drugs and osteoproliferative drugs based on their primary mechanisms of action. Anti-resorption drugs increase bone density and reduce bone turnover by inhibiting osteoclast activity. FDA-approved anti-resorption drugs include bisphosphonates, denosumab (a RANK-L inhibitor), selective estrogen receptor modulators, hormone therapy, and calcitonin. Anabolic drugs increase bone density by stimulating bone formation and include parathyroid hormone analogs and sclerotherapy binding inhibitors. The first 1-3 years after menopause are a period of rapid bone loss, accompanied by a significant increase in FSH and a sharp decline in estrogen levels; therefore, this is the most recommended period for estrogen replacement therapy. Estrogen replacement therapy using estrogen alone is more suitable for women who have had a hysterectomy or do not require endometrial protection. The combined use of estrogen and progesterone is suitable for women with an intact uterus, but unpredictable bleeding may still occur in the early stages of treatment, usually within the first 6 months. Furthermore, the 2002 WHI summary showed a significant increase in breast cancer incidence after 4 years of hormone replacement therapy, with a relative risk of 1.26 compared to the placebo group, and an absolute risk of 8 additional cases per 10,000 women-years. As for the target of elevated FSH levels, there has been a lack of effective non-injectable blocking agents.

[0004] Currently, commonly used drugs for treating PMOP in clinical practice act peripherally, targeting bone for local regulation and treatment. They typically only perform one of two effects: anti-resorption (inhibiting osteoclastosis) or osteosynthesis (enhancing osteogenic activity). During the progression of PMOP, abnormalities in both osteoclastosis and osteogenic activity occur simultaneously, leading to an imbalance in bone metabolism. Treatment often requires multi-stage combined medication designs based on the patient's current condition. Therefore, there is an urgent need to develop small-molecule oral drugs that can simultaneously enhance osteogenic activity and inhibit osteoclastosis. According to recent research, elevated FSH levels, as a major upstream pathogenic factor in PMOP, simultaneously inhibit osteogenic activity and enhance osteoclastosis. Therefore, controlling FSH holds promise for achieving more comprehensive therapeutic effects. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention aims to provide the application of an inhibitor of transcription factor C / EBPβ in the preparation of a drug for treating postmenopausal osteoporosis.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] This invention provides the application of transcription factor C / EBPβ in screening drugs that reduce postmenopausal FSH levels, wherein the drugs inhibit the expression of transcription factor C / EBPβ.

[0008] Furthermore, the drug is a small molecule compound that inhibits the expression of transcription factor C / EBPβ, a reagent that silences C / EBPβ based on RNA interference technology, or a reagent that knocks out C / EBPβ based on gene editing technology.

[0009] Furthermore, the drug is a small molecule compound represented by Formula I:

[0010] This invention also provides the use of an inhibitor of transcription factor C / EBPβ expression in the preparation of a medicament for treating postmenopausal osteoporosis.

[0011] Furthermore, the inhibitor that inhibits the expression of transcription factor C / EBPβ is a small molecule compound that inhibits the expression of transcription factor C / EBPβ, a drug that silences C / EBPβ based on RNA interference technology, or a drug that knocks out C / EBPβ based on gene editing technology.

[0012] Furthermore, the inhibitor that suppresses the expression of transcription factor C / EBPβ is a small molecule compound as shown in Formula I:

[0013] This invention also provides the use of compound CF3CN in the preparation of a medicament for treating postmenopausal osteoporosis, wherein compound CF3CN is a small molecule compound represented by formula II:

[0014] The present invention also provides a pharmaceutical composition for treating postmenopausal osteoporosis, wherein the active ingredient of the pharmaceutical composition comprises a small molecule compound represented by Formula I:

[0015] Furthermore, the active ingredient of the pharmaceutical composition also includes a small molecule compound represented by Formula II.

[0016] Furthermore, the pharmaceutical composition also includes pharmaceutically acceptable excipients.

[0017] The beneficial effects of this invention are as follows:

[0018] (1) This invention reveals for the first time that the C / EBPβ-AEP pathway participates in promoting FSHβ synthesis in a menopausal model. In a mouse PMOP model, the pro-aging transcription factor C / EBPβ regulates FSH expression at the transcriptional level. By reducing the transcription factor activity of C / EBPβ, the expression of FSH in the pituitary gland can be reduced, osteogenic differentiation can be promoted, osteoclast resorption can be inhibited, and the symptoms of PMOP can be effectively alleviated.

[0019] (2) This invention found that oral C / EBPβ-AEP small molecule inhibitor #11a can effectively inhibit the transcriptional activity of CEBPβ. By inhibiting C / EBPβ, the expression level of FSHβ in pituitary cells and the content of FSHβ in serum can be reduced, resulting in a good therapeutic effect on PMOP. #11a effectively achieves the functions of anti-bone resorption and bone formation, thus achieving coupled treatment of PMOP. It is a potential clinical oral drug with coupled function in the treatment of PMOP.

[0020] (3) The present invention found that the oral TrkB receptor agonist CF3CN can inhibit the activity of AEP (asparagine endopeptidase) by phosphorylation, thereby achieving a good therapeutic effect on PMOP. CF3CN effectively achieves the functions of anti-bone resorption and bone formation, thus achieving coupled treatment of PMOP. Attached Figure Description

[0021] Figure 1. C / EBPβ regulates FSHβ expression. (AC) C / EBPβ knockout inhibits FSHβ expression but not LHβ expression. Wild-type or C / EBPβ+ / - mice (3-4 months old) were divided into a sham-operated group (A: left) and an OVX group (A: right). Their pituitary glands were isolated, and FSHβ protein levels were detected by immunoblotting (A)(B). The mRNA level of FSHβ in the pituitary gland was detected by reverse transcription quantitative PCR (n=3) (C).

[0022] Figure 2. C / EBPβ regulates FSHβ expression. (DF) Knockout of AEP significantly reduced FSHβ expression in OVX mice, but had no effect on LHβ expression. Pituits were isolated from wild-type and AEP- / - mice (3–4 months old), and FSHβ protein (D)(E) and mRNA (F) levels in the pituitary gland were detected by immunoblotting and reverse transcription quantitative PCR (n=3). (G) Isolated rat pituitary cells expressing FSHβ and FSHR (FSH receptor). Left: Representative image of primary cultured pituitary cells, stained with DIV 7 for FSHβ (green) and FSHR (red). Right: Quantitative cell populations showing positive FSHβ or FSHR signals; data represent four independent experiments.

[0023] Figure 3. C / EBPβ regulation of FSHβ expression. (H&I) FSHβ expression was induced in primary pituitary cells by overexpressing C / EBPβ via lentivirus under different treatments. Primary cultured cells were divided into a control group and a GnRH (gonadotropin-releasing hormone, 10 nM, 6 h) treatment group. Immunoblotting and reverse transcription quantitative PCR were used to detect the protein and mRNA levels of C / EBPβ and FSHβ. (J&K) Knockdown of C / EBPβ in primary pituitary cells via lentivirus-mediated shRNA expression reduced FSHβ expression under GnRH treatment. Immunoblotting (J) and reverse transcription quantitative PCR (K) were used to detect FSHβ mRNA and protein levels. The reverse transcription quantitative PCR data in (I) and (K) represent three independent experiments. Data are presented as mean ± SEM, student-t test, *P<0.05, **P<0.01, ***P<0.001.

[0024] Figure 4. Increased FSH expression after OVX inhibition with #11a but not CF3CN. (A) Anatomical photographs of the uterus in OVX (oophorectomy) or Sham (sham surgery) mice administered solvent, #11a, or CF3CN by gavage. The OVX group showed linear atrophy of the uterus. (B) Serum FSH levels in sham and OVX mice, after gavage administration of solvent, #11a, or CF3CN to OVX mice (left), or after gavage administration of solvent or TrkB agonist R13 to BDNF- / + mice (right). N = 4–6 mice / group.

[0025] Figure 5. Increased FSH expression after OVX inhibition with #11a but not CF3CN. (C) Immunoblot analysis of FSHβ, pC / EBPβ, C / EBPβ, and AEP levels in the pituitary glands of sham, OVX+solvent, OVX+#11a, and OVX+CF3CN mice. Data are representative of three independent experiments. (D) Quantification of data from (C), n=3 for each group.

[0026] Figure 6. Increased FSH expression after OVX inhibition by #11a (but not CF3CN). (E) RT-qPCR was used to detect the mRNA levels of FSHβ and C / EBPβ in the pituitary glands of sham, OVX+solvent, OVX+#11a, and OVX+CF3CN mice, n=3 per group. GAPDH was used as an internal control. Data are presented as mean ± SEM. One-way ANOVA, *P<0.05, **P<0.01, ***P<0.001.

[0027] Figure 7. #11a promotes osteogenic differentiation and mineralization of MC3T3-E4 cells. (A) Alkaline phosphatase staining of MC3T3-E4 cells treated with BDNF, 7,8-DHF, CF3CN, or #11a for 14 days. (B) Alizarin Red S calcium staining of MC3T3-E4 cells treated with BDNF, 7,8-DHF, CF3CN, or #11a for 14 days. (C) Immunoblot analysis of CF3CN-treated MC3T3-E4 cells at different time points. (D)(E) Imaging and quantification of immunoblotting analysis of MC3T3-E4 cells treated with BDNF, 7,8-DHF, CF3CN, or #11a for 14 days (n=3, data show mean ± standard deviation, statistical detection method is one-way ANOVA). (E) AEP enzyme activity curves of MC3T3-E4 cells treated with BDNF, 7,8-DHF, CF3CN, or #11a for 14 days (n=4, data are shown as mean ± standard deviation, statistical analysis was performed using one-way ANOVA). Significance values ​​in the figure are marked as *P<0.05, **P<0.01, ***P<0.001.

[0028] Figure 8. #11a inhibits osteoclast differentiation. (A) Tartrate-resistant acid phosphatase (TRAP) staining of femoral sections from the OVX surgery group treated with sham (sham surgery) and CF3CN, #11a by gavage. Top bar: 500 μm; bottom bar: 100 μm. (B) TRAP staining of RANK-L-induced differentiated RAW264.7 cells after treatment with BDNF, 7,8-DHF, CF3CN, or #11a. Scale bar: 200 μm. (C)(D) Imaging and quantification of immunoblotting assays of differentiated RAW264.7 cells treated with BDNF, 7,8-DHF, CF3CN, or #11a (n=3, data show mean ± standard deviation, statistical detection method: one-way ANOVA). (E) AEP enzyme activity curves of RAW264.7 cells treated with BDNF, 7,8-DHF, CF3CN, or #11a for 4 days (n=4, data are shown as mean ± standard deviation, statistical analysis was performed using one-way ANOVA). (F) Representative images of anti-C / EBPβ and AEP immunohistochemical staining from distal femoral sections. Significance values ​​in the figures are marked as *P<0.05, **P<0.01, ***P<0.001.

[0029] Figure 9. Both #11a and CF3CN alleviate PMOP in mouse models by inhibiting bone turnover. (A and B) In vitro μCT assessment of femoral structure: (A) Index images of femoral trabecular structure measured by in vitro μCT scan. Scale bar shows 200 μm; (B) Quantitative analysis of μCT scan results for trabecular volume fraction (BV / TV); structural model index (SMI), number of trabeculae (Tb.N), intertrabecular spacing (Tb.Sp), and trabecular thickness (Tb.Th) (n=7, one-way ANOVA). (C) Bone mineral density (BMD) and bone mineral content (BMC) measured by DXA (n=6, one-way ANOVA). (D) Hematoxylin-eosin (he) staining of distal femoral sections. Scale bar is 500 μm. (E & F) Representative sections and statistical analysis of histological parameters of calcein dual fluorescently labeled images (n=4, one-way ANOVA). Data are expressed as mean ± SEM. One-way ANOVA, *P<0.05, **P<0.01, ***P<0.001.

[0030] Figure 10. Comparison of the effects of #11a and teriparatide on postmenopausal osteoporosis. (A) Representative images of femoral index of trabecular bone structure measured by in vitro μCT scan. In 12-week-old ovariectomized or sham-operated wild-type mice, some mice were given solvent, #11a (7.5 mg / kg / day, fed continuously for 8 weeks) or teriparatide (40 μg / kg, subcutaneously injected daily for 8 weeks), and femoral structure was assessed by in vitro μCT. (B) Statistical analysis of BV / TV, Conn.D., SMI, Tb.N, Tb.Sp, Tb.Th, Tb.Pf, BMD, and BMC in μCT scan results. Data are expressed as mean ± standard deviation. n = 3 mice per group. One-way ANOVA was performed. Significance markers in the figure: *P < 0.05, **P < 0.01, ***P < 0.001. (C) μCT cortical bone CT scan results: measurements and statistics of Ct.Ar, Ct.Th, and Ct.Ar / Tt.Ar. Data are expressed as mean ± standard deviation, n = 8 mice per group, one-way ANOVA. (D) Hematoxylin-eosin (HE) staining of distal femoral sections. Scale bar indicates 500 μm. (E) Tartrate-resistant acid phosphatase staining (trap staining) of distal femoral sections. Scale bar indicates 120 μm. Detailed Implementation

[0031] The following embodiments are merely some, not all, of the embodiments of the present invention. Therefore, the detailed descriptions of the embodiments provided below are not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0032] The structural formula of compound #11a in this invention is shown in Formula I below:

[0033] The structural formula of compound CF3CN in this invention is shown in Formula II below:

[0034] Example 1: C / EBPβ regulates FSHβ expression

[0035] Wild-type mice and C / EBPβ+ / - mice (3-4 months old) underwent sham surgery (Sham) or ovariectomy (OVX), respectively. Two weeks after the surgery, the pituitary gland was isolated, and the protein levels of FSHβ and LHβ were detected by immunoblotting (Figure 1A and 1B). The mRNA levels of FSHβ and LHβ in the pituitary gland were detected by reverse transcription quantitative PCR (Figure 1C). The results showed that C / EBPβ mediated the increase of FSHβ induced by OVX, but had no significant effect on the expression of LHβ.

[0036] Compared to wild-type mice, the level of FSHβ in the pituitary gland of AEP- / - (3-4 month old) OVX mice was also significantly decreased in immunoblotting (Fig. 2D and 2E) and reverse transcription quantitative PCR (Fig. 2F). Immunofluorescence staining of isolated primary pituitary culture cells from rats confirmed that the cells were mainly composed of cells expressing FSHβ and FSHR (FSH receptor) (Fig. 2G). Overexpression of C / EBPβ in primary pituitary cells using lentivirus, followed by control or GnRH (gonadotropin-releasing hormone, 10 nM, 6 h) treatment, was analyzed by immunoblotting (Fig. 3H) and quantitative reverse transcription PCR (Fig. 3I). The results showed that C / EBPβ overexpression upregulated FSHβ protein and mRNA levels in the control group, while GnRH treatment did not further promote FSHβ expression, suggesting that C / EBPβ is downstream of GnRH activation. Knockdown of C / EBPβ in primary pituitary cells via lentivirus-mediated shRNA reduced FSHβ expression under GnRH treatment (Figs. 3J and 3K).

[0037] Example 2: #11a instead of CF3CN inhibits the increase in FSH after OVX

[0038] By observing the uterine morphology of mice in the OVX (oophorectomy) or Sham (sham surgery) groups administered solvent, #11a, or CF3CN via gavage, the OVX group showed atrophied uterus (Figure 4A), indicating successful model establishment. ELISA results of serum FSH levels in these mice showed differences, with only #11a inhibiting the increase in FSH after OVX (Figure 4B). Immunoblot analysis of the pituitary glands of sham, OVX+solvent, OVX+#11a, and OVX+CF3CN mice showed that #11a inhibited the levels of FSHβ, pC / EBPβ, C / EBPβ, and AEP proteins in the pituitary gland during OVX, while CF3CN did not (Figures 5C and 5D). RT-qPCR reflected the inhibition of FSHβ mRNA levels by #11a (Figure 6E), indicating that this inhibition was achieved at the transcriptional level.

[0039] Example 3: #11a and CF3CN promote osteogenic differentiation and mineralization of MC3T3-E4 cells

[0040] MC3T3-E4 cell differentiation was induced using OIM (osteoblast induction medium). The medium was treated with control solvents DMSO (dimethyl sulfoxide), BDNF (50 ng / mL), 7,8DHF (0.5 μM), CF3CN (10 nM), or #11a (10 nM), with the medium changed every 3 days. After 14 days, alkaline phosphatase staining was performed. The results showed that #11a significantly promoted osteoblast differentiation (Figure 7A). After 21 days of induction, Alizarin Red S staining was performed, and the results showed that the calcium mineralization capacity of osteoblasts was also significantly improved in the #11a and CF3CN treatment groups (Figure 7B). Acute CF3CN treatment of differentiated MC3T3-E4 cells and immunoblotting analysis at different time points within 60 minutes showed that CF3CN indeed activated TrkB and its downstream signaling pathways, and also inhibited the C / EBPβ-AEP pathway through p-Akt phosphorylation of AEP (Figure 7C). Immunoblot analysis was performed on phosphorylated C / EBPβ, AEP, osteogenic differentiation activators fibronnectin, osterix, RUNX, and osteoclast differentiation inhibitor OPG. Analysis showed that both #11a and CF3CN inhibited the activation of the C / EBPβ-AEP pathway during differentiation and promoted the expression of osteoblast activating factors and OPG (Figures 7D and 7E). This indicates that they can promote osteoblast differentiation by activating these pathways, while simultaneously increasing OPG expression in osteoblasts, antagonizing RANK-L binding to RANK, and further inhibiting osteoclast differentiation. In addition, the TrkB agonists BDNF and 7,8-DHF also inhibited AEP activation through Akt, thus achieving a similar osteogenic effect. The detection of AEP enzyme activity verified that #11a, BDNF, 7,8-DHF, and CF3CN in MC3T3-E4 significantly inhibited AEP enzyme activity (Figure 7F).

[0041] Example 4: #11a and CF3CN inhibit osteoclast differentiation

[0042] #11a was dissolved in 5% DMSO and administered by gavage at a dose of 7.5 mg / kg / day, or CF3CN was dissolved in 0.5% methylcellulose and administered by gavage at a dose of 5 mg / kg / day to wild-type OVX mice. The control group received 5% DMSO via gavage at the same frequency. After 12 weeks of feeding, femoral sections were dissected for tartrate-resistant acid phosphatase staining. The staining results showed that both #11a and CF3CN significantly reduced the number of osteoclasts (Figure 8A). In a system where RAW264.7 mice were induced to differentiate into osteoclasts with RANK-L (receptor activator of NF-κB ligand) at 30 ng / mL, DMSO (dimethyl sulfoxide), BDNF (50 ng / mL), and 7,8DHF (dimethyl sulfoxide) were applied. Four days after treatment with 0.5 μM CF3CN (10 nM) or #11a (10 nM), the degree of osteoclast differentiation was detected by acid phosphatase staining. The results showed that #11a and CF3CN significantly inhibited osteoclast differentiation (Figure 8B). Immunoblotting analysis and AEP enzyme activity detection were performed on RAW264.7 mice treated with the above methods. The results showed that #11a and CF3CN successfully inhibited C / EBPβ and AEP enzyme activity and protein levels in this cell differentiation system (Figures 8C-8E). Immunohistochemical staining of bone sections from OVX mice that were administered #11a and CF3CN by gavage also showed the inhibitory effect of both on C / EBPβ and AEP (Figures 8C-8F).

[0043] Example 5: Both #11a and CF3CN alleviate PMOP in mouse models by inhibiting bone turnover.

[0044] To evaluate the efficacy of #11a and CF3CN in alleviating PMOP in a mouse model, mice were treated by gavage with #11a or CF3CN (dissolved in 5% DMSO / 0.5% methylcellulose) 4 weeks after ovariectomy at doses of 7.5 mg / kg / d (#11a) and 5 mg / kg / d (CF3CN), 6 days a week for 12 weeks. The femur was then dissected, and the femoral structure was assessed using in vitro μCT (Figure 9A). The results showed that the femoral trabecular volume fraction (BV / TV), structural model index (SMI), and connectivity coefficient (Conn.D) were significantly alleviated after treatment with #11a and CF3CN, while the number of trabeculae (Tb.N), intertrabecular spacing (Tb.Sp), and trabecular thickness (Tb.Th) did not show significant improvement (Figure 9B). Bone mineral density (BMD) and bone mineral content (BMC), measured by X-ray absorptiometry (DXA), were significantly reduced after treatment with #11a and CF3CN (Figure 9C). Hematoxylin-eosin (he) staining of distal femoral sections showed enhanced osteogenic differentiation after treatment with #11a and CF3CN, and calcein dual fluorescence labeling experiments indicated increased bone calcium deposition (Figures 9D and 9E).

[0045] Example 6: #11a has similar therapeutic effects to triparatide in a mouse PMOP model.

[0046] In 12-week-old wild-type mice that underwent ovariectomy or sham surgery, treatment with solvent (controlled diet, injected with saline), #11a (7.5 mg / kg / day, for 8 weeks) or teriparatide (40 μg / kg, subcutaneous injection daily for 8 weeks) was administered. The femur was dissected, and in vitro μCT scans were used to evaluate trabecular bone structure (Figure 10A). Measurements and statistical analyses of BV / TV, Conn.D., SMI, Tb.N, Tb.Sp, Tb.Th, Tb.Pf, BMD, and BMC parameters showed that #11a increased trabecular density and quantity, optimized morphology and structure, and effectively increased bone mass, with effects similar to teriparatide (Figure 10B). μCT Ct scans of the cortical bone, as well as measurements and statistical analyses of Ct.Ar, Ct.Th, and Ct.Ar / Tt.Ar parameters, also indicated that #11a significantly increased cortical bone thickness (Figure 10C). Meanwhile, hematoxylin-eosin (HE) staining of distal femoral sections showed that #11a increased osteoblast differentiation, and #11a significantly inhibited the differentiation of bone marrow cells into adipocytes (Fig. 10D). Tartrate-resistant acid phosphatase staining (trap staining) showed that #11a inhibited osteoclast differentiation.

[0047] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The application of transcription factor C / EBPβ in screening drugs to reduce postmenopausal FSH levels, characterized in that, The drug inhibits the expression of transcription factor C / EBPβ.

2. The application according to claim 1, characterized in that, The drug is a small molecule compound that inhibits the expression of transcription factor C / EBPβ, a reagent that silences C / EBPβ based on RNA interference technology, or a reagent that knocks out C / EBPβ based on gene editing technology.

3. The application according to claim 1, characterized in that, The drug is a small molecule compound represented by Formula I:

4. Application of inhibitors that suppress transcription factor C / EBPβ expression in the preparation of drugs for treating postmenopausal osteoporosis.

5. The application according to claim 4, characterized in that, The inhibitors that inhibit the expression of transcription factor C / EBPβ are small molecule compounds that inhibit the expression of transcription factor C / EBPβ, drugs that silence C / EBPβ based on RNA interference technology, or drugs that knock out C / EBPβ based on gene editing technology.

6. The application according to claim 4, characterized in that, The inhibitor that suppresses the expression of transcription factor C / EBPβ is a small molecule compound as shown in Formula I:

7. The use of compound CF3CN in the preparation of a drug for treating postmenopausal osteoporosis, characterized in that, The compound CF3CN is a small molecule compound represented by Formula II:

8. A pharmaceutical composition for treating postmenopausal osteoporosis, characterized in that, The active ingredient of the pharmaceutical composition includes a small molecule compound represented by Formula I:

9. The pharmaceutical composition according to claim 8, characterized in that, The active ingredient of the pharmaceutical composition also includes a small molecule compound represented by Formula II.

10. The pharmaceutical composition according to claim 8, characterized in that, The pharmaceutical composition also includes pharmaceutically acceptable excipients.

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