The miR-665/SOST Axis Regulates the Phenotypes of Bone Marrow Mesenchymal Stem Cells and Osteoporotic Symptoms in Female Mice.

Osteoporosis is a common degenerative skeletal disease among older people, especially postmenopausal women. Bone marrow mesenchymal stem cells (BMSCs), the progenitors of osteoblasts, are essential to the pathophysiology of osteoporosis. Herein, targeting miRNAs with differential expression in dysfunctional BMSCs was accomplished by bioinformatics analysis based on public databases. Target mRNAs were predicted and applied for signaling pathway and function enrichment annotations. In vitro and in vivo effects of selected miRNA on BMSC proliferation and osteogenesis were investigated, the putative binding between selected miRNA and predicted target mRNA was verified, and the co-effects of the miRNA/mRNA axis on BMSCs were determined. miRNA 665 (miR-665) was down-regulated in osteoporotic BMSCs compared with normal BMSCs and elevated in BMSCs experiencing osteogenic differentiation. In BMSCs, miR-665 overexpression promoted cell proliferation and osteogenic differentiation. miR-665 targeted the Wnt signaling inhibitor sclerostin (SOST) and inhibited SOST mRNA and protein expression. SOST overexpression inhibited BMSC cell proliferation and osteogenic differentiation. When co-transduced to BMSCs, SOST knockdown significantly reversed the effects of miR-665 on BMSCs. In ovariectomy (OVX)-induced osteoporosis model mice, OVX remarkably decreased bone mass, whereas miR-665 overexpression partially improved OVX-induced bone mass loss. miR-665 was down-regulated in osteoporotic BMSCs and up-regulated in osteogenically differentiated BMSCs. In conclusion, the miR-665/SOST axis modulates BMSC proliferation, osteogenic differentiation, and OVX-induced osteoporosis in mice, possibly through Wnt signaling.

Synthesis of α-allenic aldehydes/ketones from homopropargylic alcohols using a visible-light irradiation system.

A visible-light irradiation tandem oxidative aryl migration/carbonyl formation reaction, mediated by K2S2O8 and visible-light photoredox catalysis, has been discovered. The presented transformation provides a straightforward access to important α-allenic aldehyde/ketone derivatives from readily available homopropargylic alcohol derivatives in a regioselective manner of 1,4-aryl shift concomitant with carbonyl formation. The operational simplicity and broad substrate scope demonstrate the great potential of this method for the synthesis of highly functional α-allenic aldehyde/ketone derivatives.

Comparison of Lycium barbarum fruits polysaccharide from different regions of China by acidic hydrolysate fingerprinting-based HILIC-ELSD-ESI-TOF-MS combined with chemometrics analysis.

INTRODUCTION: Lycium barbarum is an edible fruit widely used in herbal medicines and as a functional food. Polysaccharide is one of the most important active ingredients. Only L. barbarum grown in the Ningxia region of China are officially recognised as suitable for use in traditional Chinese medicine, but the systematic comparison of L. barbarum polysaccharide between Ningxia and the other growing regions of China has been rarely reported. OBJECTIVE: To compare the difference of L. barbarum polysaccharide from different grown regions of China. METHODS: A chemical fingerprint of L. barbarum polysaccharide hydrolysates was established based on controlled acidolysis combined with hydrophilic interaction liquid chromatography-evaporative light scattering detection-electrospray ionisation-time-of-flight-mass spectrometry (HILIC-ELSD-ESI-TOF-MS). Then, it was employed for the comparison of L. barbarum samples from different geographical origins of China combined with chemometrics analysis. RESULTS: Six monosaccharides [rhamnose (Rha), xylose (Xyl), arabinose (Ara), mannose (Man), glucose (Glu), galactose (Gal)] were qualitatively and quantitatively determined and four glycoconjugates were preliminarily identified from the hydrolysates. Content determination for the polysaccharide and monosaccharide indicated obvious geographical features. The HILIC-ELSD fingerprint combined with partial least squares-discriminant analysis (PLS-DA) was able to differentiate L. barbarum samples from Ningxia, Xinjiang, Gansu and Qinghai regions with 89.19% classification accuracy. Orthogonal projection to latent structure discriminant analysis (OPLS-DA) was able to differentiate between samples from Ningxia and those from the other three growing regions, polysaccharide and Ara were the potential chemical markers. CONCLUSIONS: These findings form the basis of a reliable method to trace the region of origin of L. barbarum sample and thereby, improve the quality control of L. barbarum therapeutic polysaccharides.

RNA adenosine modifications related to prognosis and immune infiltration in osteosarcoma.

BACKGROUND: RNA adenosine modifications, which are primarily mediated by "writer" enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognostic role of these genes in osteosarcoma (OS) remain unclear. METHODS: Univariate and multivariate Cox analyses were used to construct the RMW signature for OS using Target datasets. RMW expression in OS tissue was detected by qPCR analysis. Xcell and GSVA were used to determine the relationship between RMWs and immune infiltration. The DGIdb and CMap databases were used for drug prediction. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS. RESULTS: A 3-RMW (CSTF2, ADAR and WTAP) prognostic signature in OS was constructed using the Target dataset and verified using GEO datasets and 63 independent OS tissues via qPCR analysis. High-risk OS patients had poor overall survival, and the prognostic signature was an independent prognostic factor for OS. Functional studies showed that tumour-, metabolism-, cell cycle- and immune-related pathways were related to high risk. Next, we found that RMW-derived high-risk patients exhibited increased infiltration of M2 macrophages and cDCs. Furthermore, we predicted the potential drugs for OS using the DGIdb and CMap databases. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS by repressing cell growth and inducing cell cycle arrest at the G1 phase. CONCLUSION: The 3-RWM-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS by repressing OS cell growth and the cell cycle.

LncRNA-ROR/microRNA-185-3p/YAP1 axis exerts function in biological characteristics of osteosarcoma cells.

AIM: The co-expression network of long non-coding RNA ROR (lncRNA-ROR) and microRNA-185-3p (miR-185-3p) has not been focused on osteosarcoma. Therein, this work was initiated to uncover lncRNA-ROR and miR-185-3p functions in osteosarcoma. METHODS: LncRNA-ROR, miR-185-3p and Yes-associated protein 1 (YAP1) expression in osteosarcoma tissues and cells were detected. The screened cells (MG63 and U2OS) were transfected with decreased and/or increased lncRNA-ROR and miR-185-3p to explore osteosarcoma progression. Tumor growth was detected by tumor xenografts in mice. RESULTS: Up-regulated lncRNA-ROR and YAP1 and down-regulated miR-185-3p were found in osteosarcoma. LncRNA ROR knockdown or miR-185-3p overexpression inhibited osteosarcoma cell progression while lncRNA ROR elevation or miR-185-3p inhibition presented the opposite effects. Function of lncRNA ROR was rescued by miR-185-3p and regulated the growth and metastasis of osteosarcoma cells via modulating YAP1, the target gene of miR-185-3p. CONCLUSION: This work illustrates that lncRNA-ROR down-regulation or miR-185-3p up-regulation inhibits osteosarcoma progression via YAP1 repression.

Mixed polysaccharides derived from shiitake mushroom, Poriacocos, Ginger, and Tangerine peel prevent the H1N1 virus infections in mice.

The pandemic influenza A (H1N1) virus spread globally and posed one of the most serious global public health challenges. The traditional Chinese medicine is served as a complementary treatment strategy with vaccine immunization. Here, we demonstrated that the mixed polysaccharides (MPs) derived from shiitake mushroom, poriacocos, ginger, and tyangerine peel prevent the H1N1 virus infections in mice. MP pretreatment attenuated H1N1 virus-induced weight loss, clinical symptoms, and death. The lymphocytes detection results showed that the CD3+, CD19+, and CD25+ cell proportions were upregulated in thymus under MP pretreatment. Besides, MP pretreatment reduced the inflammatory cell infiltration and increased the cell proportions of CD19+, CD25+, and CD278+ in lung. However, MP treatment have no effective therapeutic effect after H1N1 virus challenge. The current study suggested that pretreatment with MPs could attenuate H1N1 virus-induced lung injury and upregulate humoral and cellular immune responses in nonimmunized mice.

Spectrum-effect relationship between fingerprints and hemopoietic effects of small molecular fraction of Polygoni Multiflori radix praeparata.

Polygoni multiflori Radix Praeparata (PMRP) is a traditional medicine used for nourishing essence and blood in China. However, it is unclear which PMRP compounds are responsible for its hematopoietic effect. In this study, spectrum-effect relationship was used to discovery potential hematopoietic compounds. The fingerprints of 20 PMRP batches were established by HPLC and the hematopoietic effect was determined using red blood cell, hemoglobin, hematocrit, and platelet indexes in aplastic anemia model mice. The spectrum-effect relationship between common peaks and hematopoietic efficacy values was established using gray relational analysis and partial least squares analysis. Spectrum-effect relationship results showed that peaks 21 (emodin-8-O-(6´-O-acetyl)-ß-D-glucoside), 15 (2, 3, 5, 4'-tetrahydroxystilbene-2-O-di-glucoside), 16 (cis-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside), 11 (unknown), 20(unknown, 12 (epicatechin), 29 (carboxyl emodin), and 31 (emodin) in the fingerprints were closely related to the hematopoietic effect. This work successfully established the spectrum-effect relationship between PMRP hematopoietic effect and its fingerprints, which can be used to explain the material basis for the PMRP hematopoietic effect.

Alkaline Extraction, Structural Characterization, and Bioactivities of (1→6)-ß-d-Glucan from Lentinus edodes.

The purpose of this study is to develop a robust approach to obtain ß glucans from Lentinus edodes and to characterize their structural and biological properties for sustainable utilization. The alkali extraction was optimized with an orthogonal experimental design, and a concise process for obtaining specific targeting polysaccharides from Lentinus edodes was developed in this study. After purification with a Q-Sepharose Fast Flow strong anion-exchange column, the monosaccharide composition, a methylation analysis, and NMR spectroscopy were employed for their structural characterizations. LeP-N2 was found to be composed of (1→6)-ß-d-glucans with minor ß-(1→3) glucosidic side chains. Atomic force microscopy (AFM) and high-performance gel permeation chromatography-refractive index-multi-angle laser light scattering (HPGPC-RI-MALLS) also revealed LeP-N2 exhibiting a compact unit in aqueous solution. This (1→6)-ß-d-glucan was tested for antioxidant activities with IC50 at 157 µg/mL. Moreover, RAW 264.7 macrophage activation indicated that the release of nitric oxide (NO) and reactive oxygen species (ROS) was markedly increased with no cytotoxicity at a dose of 100 µg/mL. These findings suggest that the (1→6)-ß-d-glucans obtained from Lentinus edodes could serve as potential agents in the fields of functional foods or medicine.

miR-194 Suppresses Proliferation and Migration and Promotes Apoptosis of Osteosarcoma Cells by Targeting CDH2.

BACKGROUND/AIMS: Studies have shown that miR-194 functions as a tumour suppressor and is associated with tumour growth and metastasis. This study intends to uncover the mechanism of tumour suppression by miR-194. The expression of miR-194 in osteosarcoma cell lines and tissues were monitored by real-time PCR. METHODS: The proliferation ability was examined by MTT assay. Migration and apoptosis of cells were monitored by migration assay and flow cytometry, respectively. The regulation of miR-194 on CDH2 was determined by luciferase assays and western blot assays. RESULTS: The results showed that miR-194 was significantly reduced in osteosarcoma compared with that in normal bone tissue. Overexpression of miR-194 significantly attenuated the proliferation and migration and induced the apoptosis of osteosarcoma cells. Furthermore, we demonstrated that miR-194 has inhibited the malignant behaviour of osteosarcoma by downregulating CDH2 expression. CONCLUSIONS: These findings suggested that miR-194 may act as a tumour suppressor in osteosarcoma. miR-194/CDH2 may be a novel therapeutic target in the treatment of osteosarcoma.

An Asparagus polysaccharide fraction inhibits MDSCs by inducing apoptosis through toll-like receptor 4.

Despite decades of research, malignant tumors are extremely difficult to eliminate with conventional methods. Although surgical resection potentially eradicates the problem, only a few cases are suitable for operation, and other approaches often involve harmful consequences. Revolutionary methods are desperately needed to improve patient outcomes and diminish harmful side effects. Myeloid-derived suppressor cells (MDSCs), downregulators of the innate and adaptive immune systems, have been widely studied over the past 2 decades. MDSCs inhibit the antitumor immune response by suppressing T cell proliferation, cytokine production, and tumor cell killing. With MDSCs becoming novel targets in cancer therapy, our research has focused on the anti-MDSC function of Asparagus polysaccharide (AP), extracted from asparagus, a traditional Chinese herb. In this study, we have used MDSCs isolated from the spleen of mice with colon cancer as an in vitro model to assess the efficacy of AP. Treatment of MDSCs with AP significantly decreased cell proliferation and induced apoptotic cell death through a toll-like receptor 4 dependent way. Subsequent studies showed that the AP treatment enhanced the expression of Bax and Caspase-9 and inhibited the expression of Bcl-2, suggesting that AP induced apoptosis in the MDSCs via the intrinsic pathway. Altogether, the results showed that AP exhibited a significant anti-MDSC activity and attenuated suppression of the antitumor immune response, thereby indicating its potential use in cancer therapy.

[Rapidly identify oligosaccharides in Morinda officinalis by UPLC-Q-TOF-MSE].

In this paper, an approach was applied for separation and identification of oligosaccharides in Morinda officinalis How by Ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) with collision energy. The separation was carried out on an ACQUITY UPLC BEH Amide C18(2.1mm×100 mm，1.7 µm) with gradient elution using acetonitrile(A) and water(B) containing 0.1% ammonia as mobile phase at a flow rate of 0.2 mL·min⁻¹. The column temperature was maintained at 40 °C. The information of accurate mass and characteristic fragment ion were acquired by MSE in ESI negative mode in low and high collision energy. The chemical structures and formula of oligosaccharides were obtained and identified by the software of UNIFI and Masslynx 4.1 based on the accurate mass, fragment ions, neutral losses, mass error, reference substance, isotope information, the intensity of fragments, and retention time. A total of 19 inulin oligosaccharide structures were identified including D(+)-sucrose, 1-kestose, nystose, 1F-fructofuranosyl nystose and other inulin oligosaccharides (DP 5-18). This research provided important information about the inulin oligosaccharides in M. officinalis. The results would provide scientific basis for innovative utilization of M. officinalis.

[Rapid identification of geographical origins and determination of polysaccharides contents in Ganoderma lucidum based on near infrared spectroscopy and chemometrics].

Near infrared spectroscopy combined with chemometrics methods was used to distinguish Ganoderma lucidum samples collected from different origins, and a prediction model was established for rapid determine polysaccharides contents in these samples. The classification accuracy for training dataset was 96.87%, while for independent dataset was 93.33%; as for the prediction model, 5-fold cross-validation was used to optimize the parameters, and different signal processing methods were also optimized to improve the prediction ability of the model. The best square of correlation coefficients for training dataset was 0.965 4, and 0.851 6 for validation dataset; while the root-mean-square deviation values for training dataset and validation dataset were 0.018 5 and 0.023 6, respectively. These results showed that combining near infrared spectroscopy with suitable chemometrics approaches could accuracy distinguish different origins of G. lucidum samples; the established prediction model could precious predict polysaccharides contents, the proposed method can help determine the activity compounds and quality evaluation of G. lucidum.

A polysaccharide from Dictyophora indusiata inhibits the immunosuppressive function of cancer-associated fibroblasts.

Reversing the function of cancer-associated fibroblasts (CAFs) may improve the efficacy of cancer therapy. Here, we isolated a novel polysaccharide from Dictyophora indusiata (ZSP4) and examined its effects on the function of prostate CAFs. The supernatant of prostate CAFs can stimulate the proliferation of immune cells and inhibit the growth of CD4+/CD8+ T cells. However, after ZSP4 stimulation, the functions of prostate CAFs were inhibited. The mechanism experiment shows that ZSP4 can stimulate prostate CAFs by down-regulating the expression of α-smooth muscle actin. Polysaccharides extracted from Dictyophora indusiata stimulate the proliferation of immune cells and reverse the immune-suppressive functions of prostate CAFs, shedding new light on the development of novel anticancer strategies. The endocrine therapy used to treat prostate cancer aims to eliminate androgenic activity from prostatic tissue; these therapies are painful and of poor therapeutic effect. In this study, we found that polysaccharides extracted from Dictyophora indusiata may affect the micro-environment of tumours and inhibit the growth of the tumours. Our results suggest that polysaccharides may modulate negative immune regulation and enhance antitumour immunity, which is important for clinical therapy.

Selective synthesis of polyfunctionalized pyrido[2,3-b]indoles by multicomponent domino reactions.

A series of novel polyfunctionalized pyrido[2,3-b]indoles were synthesized by three- or four-component domino reactions under microwave irradiation. This protocol has the advantages of readily available starting materials, short reaction times, high yields, easy workup, and high chemo- and regioselectivities.

Salidroside protects Caenorhabditis elegans neurons from polyglutamine-mediated toxicity by reducing oxidative stress.

Polyglutamine (polyQ) aggregation plays a pivotal role in the pathological process of Huntington's disease and other polyQ disorders. Therefore, strategies aiming at restoring dysfunction and reducing stresses mediated by polyQ toxicity are of therapeutic interest for proteotoxicity diseases. Salidroside, a glycoside from Rhodiola rosea, has been shown to have a variety of bioactivities, including antioxidant activity. Using transgenic Caenorhabditis elegans models, we show here that salidroside is able to reduce neuronal death and behavioral dysfunction mediated by polyQ expressed in ASH neurons, but the neuroprotective effect is not associated with prevention of polyQ aggregation per se. Further experiments reveal that the neuroprotective effect of salidroside in C. elegans models involves its antioxidant capabilities, including decrease of ROS levels and paraquat-induced mortality, increase of antioxidant enzyme activities and reduction of lipid peroxidation. These results demonstrate that salidroside exerts its neuroprotective function against polyQ toxicity via oxidative stress pathways.

Genetic Evidence of SpGH9A3 in Leaf Morphology Variation of Spathiphyllum 'Mojo'.

Leaves play a crucial role as ornamental organs in Spathiphyllum, exhibiting distinct differences across various Spathiphyllum varieties. Leaf development is intricately linked to processes of cell proliferation and expansion, with cell morphology often regulated by plant cell walls, primarily composed of cellulose. Alterations in cellulose content can impact cell morphology, subsequently influencing the overall shape of plant organs. Although cellulases have been shown to affect cellulose levels in plant cells, genetic evidence linking them to the regulation of leaf shape remains limited. This study took the leaves of Spathiphyllum 'Mojo' and its somatic variants as the research objects. We screened four cellulase gene family members from the transcriptome and then measured the leaf cellulose content, cellulase activity, and expression levels of cellulase-related genes. Correlation analysis pinpointed the gene SpGH9A3 as closely associated with leaf shape variations in the mutant. Green fluorescent fusion protein assays revealed that the SpGH9A3 protein was localized to the cell membrane. Notably, the expression of the SpGH9A3 gene in mutant leaves peaked during the early spread stage, resulting in smaller overall leaf size and reduced cellulose content upon overexpression in Arabidopsis.

Over-expression of regulator of G protein signaling 5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. The regulator of G-protein signaling 5 (RGS5) has been reported to be highly expressed in some malignant tumors. However, its expression and role in HCC has not been reported. METHODS: The expression of RGS5 was examined in liver cancer tissues and cell lines by real-time quantitative PCR. The cell migration and invasion was investigated by wound healing and transwell invasion assay. The epithelial-mesenchymal transition markers were detected by Western blotting or immunofluorescence. RESULTS: We observed that RGS5 is over-expressed in most of liver cancer tissue samples and cell lines compared with matched normal samples. Further analysis showed that the over-expression of RGS5 is associated with liver cancer recurrence, venous infiltration, and patients' poor survival. Next, we found that knockdown of RGS5 significantly inhibits liver cancer cell migration and invasion in highly invasive liver cancer cells. Furthermore, we found that over-expression of RGS5 induces epithelial-mesenchymal transition in epithelial liver cancer cells. CONCLUSIONS: These results indicate that over-expression of RGS5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in HCC.

Microwave-assisted improved synthesis of pyrrolo[2,3,4-kl]acridine and dihydropyrrolo[2,3,4-kl]acridine derivatives catalyzed by silica sulfuric acid.

An improved synthesis of multifunctionalized pyrrolo[2,3,4-kl]acridine derivatives with different substituted patterns using silica sulfuric acid (SSA) as a heterogeneous catalyst under microwave irradiation conditions was developed. The reaction could be conducted by using readily available and inexpensive substrates within short periods of 12-15 min. under microwave irradiation. Compared with the conventional methods, the remarkable advantages of this method are milder reaction conditions, operational simplicity, higher yields, short reaction times, and an environmentally friendly procedure.

Clinical characteristics and long-term follow-up outcomes of myelin oligodendrocyte glycoprotein antibody-associated disease in Han Chinese participants.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated inflammatory demyelinating disease of the central nervous system. This study aimed to delineate the clinical manifestations, imaging features, and long-term outcomes in Chinese patients with MOGAD and analyze the recurrence-associated factors. The phenotypic and neuroimaging characteristics of 15 Han Chinese patients with MOGAD were retrospectively analyzed. Demyelinating attacks, MOG antibodies in the cerebrospinal fluid/serum, response to immunotherapy, follow-up outcomes, and recurrence-associated factors were recorded. The median age at disease onset was 34 years (range, 4-65 years). The most common initial presentations included vision loss (10/15, 66.7%) and seizures (5/15, 33.3%). Serum MOG-Ab titers in 14/15 cases were higher than those in the cerebrospinal fluid and were detected in 3/6 relapsed patients. Brain magnetic resonance imaging during acute attacks showed lesions in 10/15 patients (66.7%), mostly in the cortex/subcortical white matter (5/15, 33.3%). Recurrence occurred in 6/15 patients (40.0%); in 4 patients, recurrence occurred shortly after immunotherapy discontinuation. Residual neurological deficits were present in 5/15 patients (33.3%), including visual impairment, incapacitation, cognitive impairment, and speech reduction. Optic neuritis was the most common clinical manifestation of MOGAD. magnetic resonance imaging findings were heterogeneous and the cerebral cortex/subcortical white matter was the most susceptible brain region. Although patients in the acute phase responded well to methylprednisolone pulse therapy, the long-term recurrence rate was high. Consistently detected serum MOG antibodies and inappropriate maintenance immunotherapy may be associated with recurrence, and residual neurological deficits should not be ignored.

The metabolic score of insulin resistance is positively correlated with bone mineral density in postmenopausal patients with type 2 diabetes mellitus.

The prevalence of type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP) is increasing yearly. Early prevention, detection and treatment of OP are important in postmenopausal patients with T2DM. This study aimed to explore the correlation between insulin resistance and bone mineral density (BMD), and OP in postmenopausal patients with T2DM. In this study, postmenopausal patients with T2DM who visited our hospital from January 2021 to March 2022 were divided into the OP group (n = 91) and non-OP group (n = 119) according to whether they were complicated with OP or not. The general data of patients, BMD, blood routine, glucose metabolism, lipid metabolism, liver and kidney function indexes were collected, and the homeostatic model assessment for IR (HOMA-IR), the triglyceride-glucose (TyG) index and the metabolic score for IR (METS-IR) were calculated. A weighted multivariate linear regression model assessed the correlation between insulin resistance (IR) related indexes and lumbar spine, femoral neck, and hip BMD. A weighted logistic regression model assessed the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between the IR-related indexes and OP risk. The nonlinear relationship was also evaluated by smooth curve fitting (SCF) and a weighted generalized additive model (GAM). Moreover, the Receiver-operating characteristics (ROC) curve was used to analyze the predictive efficiency of METS-IR in postmenopausal patients with T2DM with OP. HOMA-IR, TyG, and METS-IR in the OP group were lower than those in the non-OP group (all P < 0.05). Weighted multiple linear regression after adjusting covariates showed that METS-IR was positively correlated with the lumbar spine, femoral neck, and hip BMD (ßMETS-IR = 0.006,0.005,0.005, all P < 0.001). The results of weighted Logistic regression and GAM showed that when METS-IR < 44.5, each unit of increased METS-IR value was associated with a decreased OP risk of 12% (P = 0.002). When METS-IR ≥ 44.5, there was no significant correlation between METS-IR and the risk of OP (OR = 1.00, P = 0.934). Similar trends were not observed in HOMA-IR and TyG. The ROC suggested helpful discriminative power of the METS-IR index for T2DM. We confirmed that METS-IR, as a novel alternative marker of IR, had a positive association with BMD in postmenopausal patients with T2DM, and METS-IR was a protective factor for OP in a specific range.