Therapy For Postmenopausal Osteoporosis Research Articles

Enhancing postmenopausal osteoporosis: a study of KLF2 transcription factor secretion and PI3K-Akt signaling pathway activation by PIK3CA in bone marrow mesenchymal stem cells

IntroductionMesenchymal stem cells can develop into osteoblasts, making them a promising cell-based osteoporosis treatment. Despite their therapeutic potential, their molecular processes are little known. Bioinformatics and experimental analysis were used to determine the molecular processes of bone marrow mesenchymal stem cell (BMSC) therapy for postmenopausal osteoporosis (PMO).Material and methodsWe used weighted gene co-expression network analysis (WGCNA) to isolate core gene sets from two GEO microarray datasets (GSE7158 and GSE56815). GeneCards found PMO-related genes. GO, KEGG, Lasso regression, and ROC curve analysis refined our candidate genes. Using the GSE105145 dataset, we evaluated KLF2 expression in BMSCs and examined the link between KLF2 and PIK3CA using Pearson correlation analysis. We created a protein-protein interaction network of essential genes involved in osteoblast differentiation and validated the functional roles of KLF2 and PIK3CA in BMSC osteoblast differentiation in vitro.ResultsWe created 6 co-expression modules from 10 419 differentially expressed genes (DEGs). PIK3CA, the key gene in the PI3K-Akt pathway, was among 197 PMO-associated DEGs. KLF2 also induced PIK3CA transcription in PMO. BMSCs also expressed elevated KLF2. BMSC osteoblast differentiation involved the PI3K-Akt pathway. In vitro, KLF2 increased PIK3CA transcription and activated the PI3K-Akt pathway to differentiate BMSCs into osteoblasts.ConclusionsBMSCs release KLF2, which stimulates the PIK3CA-dependent PI3K-Akt pathway to treat PMO. Our findings illuminates the involvement of KLF2 and the PI3K-Akt pathway in BMSC osteoblast development, which may lead to better PMO treatments.

Vascular and renal calcification as a consequence of high-dose calcium and vitamin D drugs

Calcium-containing drugs occupy an important place in the list of anti-osteoporotic agents. Their consumption, often in combination with high doses of vitamin D, has increased significantly over the last couple of decades. Cases of uncontrolled intake of the macronutrient have become more frequent. Aggressive advertising of high-dose calcium supplements with calciferol of foreign production on television played its role in this. Nowadays doctors of various specialties have to face more and more often the consequences of using such preparations. The article describes the mechanism of calcium deposits formation in vessels and kidneys against the background of calcium supplementation. The results of large-scale studies proving the close relationship between high intake of calcium and vitamin D with calcification of vessels, development of cardiovascular diseases and nephrolithiasis are presented. Doubts are raised about the validity and necessity of high-dose calcium supplements in the treatment of skeletal diseases. The possibilities of successful therapy of postmenopausal osteoporosis without the use of such agents are presented on the example of the preparation Osteo-Vit D3, which does not contain calcium and high doses of calciferol, but increases the mineral density of bone tissue and reduces the volume of calcificates in blood vessels and kidneys.

Follicle-stimulating hormone accelerates osteoclast migration by enhancing methyltransferase-like 3-mediated m6A methylation of cathepsin K.

Follicle-stimulating hormone (FSH) accelerates osteoporosis in postmenopausal women, while the underlying mechanism remains uncharacterized. N6-methyladenosine (m6A) is one of the most important regulations in the development of osteoporosis. In this study, we aimed to investigate the role of FSH in m6A modification and osteoclast function. Here, we showed that FSH upregulated m6A levels in osteoclasts via stimulating methyltransferase-like 3 (METTL3) protein expression. FSH enhanced osteoclast migration, while the knockdown of METTL3 eliminated this enhancement. Both MeRIP-seq and RNA sequencing identified that cathepsin K (CTSK) is the potential downstream target of METTL3. Knockdown of CTSK reduced FSH-upregulated osteoclast migration. Furthermore, silencing METTL3 decreased CTSK mRNA stability. Finally, FSH induced phosphorylation of cyclic-AMP response element-binding protein (CREB), while silencing of CREB attenuated the effects of FSH on the promoter transcriptional activity of Mettl3 and CTSK/METTL3 protein. Taken together, these findings indicate that FSH promotes osteoclast migration via the CREB/METTL3/CTSK signaling pathway, which may provide a potential target for suppressing osteoclast mobility and postmenopausal osteoporosis therapy.

Comparative efficacy of acupuncture-related therapy for postmenopausal osteoporosis: protocol for Bayesian network meta-analysis

IntroductionThe review aims to conduct the first network meta-analysis to comprehensively evaluate the application of multiple acupuncture techniques in patients with postmenopausal osteoporosis, ranking the best acupuncture treatment and providing...

Raman spectroscopy as a tool for monitoring osteoporosis therapy in postmenopausal osteoporosis

AbstractBisphosphonate‐based pharmacological therapy of osteoporosis reduces risk of fracture, but modulation of bone mineral density does not solely explain this. Additional bone quality aspects affecting fragility need to be better understood, alongside methods to monitor them. Systemic factors that influence bone collagen remodelling also remodel keratin in parallel processes. In this study, human fingernail clippings from subjects with and without bone active pharmaceutical intervention are compared. A discriminant model was able to distinguish between the nails from patients that were treatment‐naive and treated with an area under the curve of 71% in the test set. A time series of changes relative to baseline revealed that after 1 year, the scores of the treated group (95 confidence interval 37% to 377% change) differed from both the 12 week measurements (−198% to 34%) and scores from untreated subjects (−92% to −674%). Analysis of the spectral differences and model coefficients revealed features that were inverse to those observed in three previous osteoporosis models, indicating that treatment was reverting damaged protein structure. This study provides preliminary evidence that bone active medication systemically influences keratin structure in humans and provides some discussion on the underlying mechanism. The study demonstrates that bisphosphonates have a direct influence on protein structure, warranting further investigation of these effects.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Retracted: Clinical Efficacy and Safety Evaluation of Calcitriol Combined with Bisphosphonates in the Therapy of Postmenopausal Osteoporosis: Based on a Retrospective Cohort Study.

[This retracts the article DOI: 10.1155/2022/2711938.].

Effects of ligandrol as a selective androgen receptor modulator in a rat model for osteoporosis.

The selective androgen receptor modulator ligandrol (LGD-4033 or VK5211) has been shown to improve muscle tissue. In the present study, the effect of ligandrol on bone tissue was investigated in ovariectomized rat model. Three-month-old Sprague Dawley rats were either ovariectomized (OVX, n = 60) or left intact (NON-OVX, n = 15). After 9weeks, OVX rats were divided into four groups: untreated OVX (n = 15) group and three OVX groups (each of 15 rats) treated with ligandrol orally at doses of 0.03, 0.3, or 3mg/kg body weight. After five weeks, lumbar vertebral bodies (L), tibiae, and femora were examined using micro-computed tomographical, biomechanical, ashing, and gene expression analyses. In the 3-mg ligandrol group, bone structural properties were improved (trabecular number: 38 ± 8 vs. 35 ± 7 (femur), 26 ± 7 vs. 22 ± 6 (L), 12 ± 5 vs. 6 ± 3 (tibia) and serum phosphorus levels (1.81 ± 0.17 vs.1.41 ± 0.17mmol/l), uterus (0.43 ± 0.04 vs. 0.11 ± 0.02g), and heart (1.13 ± 0.11 vs. 1.01 ± 0.08g) weights were increased compared to the OVX group. Biomechanical parameters were not changed. Low and medium doses did not affect bone tissue and had fewer side effects. Body weight and food intake were not affected by ligandrol; OVX led to an increase in these parameters and worsened all bone parameters. Ligandrol at high dose showed a subtle anabolic effect on structural properties without any improvement in biomechanical properties of osteoporotic bones. Considering side effects of ligandrol at this dose, its further investigation for the therapy of postmenopausal osteoporosis should be reevaluated.

Identifying therapeutic biomarkers of zoledronic acid by metabolomics.

Zoledronic acid (ZOL) is a potent antiresorptive agent that increases bone mineral density (BMD) and reduces fracture risk in postmenopausal osteoporosis (PMOP). The anti-osteoporotic effect of ZOL is determined by annual BMD measurement. In most cases, bone turnover markers function as early indicators of therapeutic response, but they fail to reflect long-term effects. We used untargeted metabolomics to characterize time-dependent metabolic shifts in response to ZOL and to screen potential therapeutic markers. In addition, bone marrow RNA-seq was performed to support plasma metabolic profiling. Sixty rats were assigned to sham-operated group (SHAM, n = 21) and ovariectomy group (OVX, n = 39) and received sham operation or bilateral ovariectomy, respectively. After modeling and verification, rats in the OVX group were further divided into normal saline group (NS, n = 15) and ZOL group (ZA, n = 18). Three doses of 100μg/kg ZOL were administrated to the ZA group every 2weeks to simulate 3-year ZOL therapy in PMOP. An equal volume of saline was administered to the SHAM and NS groups. Plasma samples were collected at five time points for metabolic profiling. At the end of the study, selected rats were euthanatized for bone marrow RNA-seq. A total number of 163 compound were identified as differential metabolites between the ZA and NS groups, including mevalonate, a critical molecule in target pathway of ZOL. In addition, prolyl hydroxyproline (PHP), leucyl hydroxyproline (LHP), 4-vinylphenol sulfate (4-VPS) were identified as differential metabolites throughout the study. Moreover, 4-VPS negatively correlated with increased vertebral BMD after ZOL administration as time-series analysis revealed. Bone marrow RNA-seq showed that the PI3K-AKT signaling pathway was significantly associated with ZOL-mediated changes in expression (adjusted-p = 0.018). In conclusion, mevalonate, PHP, LHP, and 4-VPS are candidate therapeutic markers of ZOL. The pharmacological effect of ZOL likely occurs through inhibition of the PI3K-AKT signaling pathway.

Does the VDR gene polymorphism influence the efficacy of denosumab therapy in postmenopausal osteoporosis?

One of the challenges of personalized medicine is a departure from traditional pharmacology toward individualized, genotype-based therapies. Postmenopausal osteoporosis is a prevalent condition requiring intensive treatment, whose effects are measurable only after a long time, and the goal is bone fracture prevention. This study aimed to determine the influence of VDR gene variation on anti-osteoporotic one-year treatment with denosumab in 63 Polish women with postmenopausal osteoporosis. The correlation between bone mineral density (BMD) of the lumbar vertebral column (L1-L4) and femoral neck, and genotype distributions for the ApaI, BsmI, FokI, and TaqI variants of the VDR gene was analyzed. Bone fractures during denosumab therapy were also investigated. In the case of the Bsml polymorphism, female patients with BB and Bb genotypes had statistically significantly higher values of BMD and T-score/Z-score indicators, which persisted after a year of denosumab treatment. Our results indicated that the Bsml polymorphism contributes to better bone status, and, consequently, to more efficient biological therapy. The study did not reveal significant differences between changes (delta) in BMD and genotypes for the analyzed VDR gene loci. In the entire study group, one bone fracture was observed in one patient throughout the yearlong period of denosumab therapy. BB and Bb genotypes of the Bsml polymorphism of the VDR gene determine higher DXA parameter values both before and after one-year denosumab therapy in postmenopausal women with osteoporosis.

Age-specific bone turnover prevalence in women with post-menopausal osteoporosis: possibilities of traditional plant therapy during COVID-19 pandemic

Post-menopausal osteoporosis is a chronic age-related illness marked by a decrease of bone density and quality, as well as a higher risk of fragility fractures. Fragility fractures are recognized to have a major impact on individuals and society both personal and financially. In recent years, it has been a hidden epidemic impacting over 200 million people globally. It is claimed that one osteoporosis fracture happens every three seconds throughout the world. The termination of ovarian hormone production, which causes rapid bone loss, puts postmenopausal women at greater risk of developing osteoporosis. The gradual changes in structure, quality and density of the bones lead to the fracture and a rise in morbidity and death among menopausal women. Interventions that enhance a woman’s well-being and quality of life by reducing the intensity and frequency of post-menopausal osteoporosis. Hormone therapy is helpful in managing menopausal symptoms; nevertheless, it has been linked to a number of potentially significant side effects, including the development of ovarian and breast cancer. As a result, there has been an increase in demand for alternative treatment options. Plant species with potential antiosteoporosis characteristics are highlighted and further discussed in order to aid future medication development for treating this illness. Many plants and there components have been demonstrated to have antiosteoporosis action based on a vast number of chemical and pharmacological studies. Plant-derived molecules have lately piqued the curiosity of researchers working on novel medicinal agents. As a result, therapeutic interventions that can delay reduce or prevent bone loss in ageing people, especially postmenopausal women, are essential to a person’s well-being and quality of life. The plants included in this review are those that have been frequently used in traditional medicine and have shown clinical efficacy in the management of post-menopausal osteoporosis. While numerous plants can prevent and treat osteoporosis, only a fraction of plants have been discussed, including their origin, active components, and pharmacological activity, we evaluated the challenges and methods utilized in the therapy of postmenopausal osteoporosis during the COVID-19 pandemic.

Selective estrogen receptor modulators in post-menopausal osteoporosis

Osteoporosis (OP) is a chronic disease that occurs when the balance between the processes of bone formation and resorption is lost. OP is characterized by a decrease in bone quality and an increased risk of fractures. In post-menopausal women, as a result of decreased estrogen levels, there is bone loss. Hormone replacement therapy was initially used for the management of OP in post-menopausal women but was soon abandoned due to the occurrence of significant side effects. This shifted research toward the development of a class of drugs called selective estrogen receptor modulators (SERMs). These drugs always act through estrogen receptors (ERs), but as agonists or antagonists depending on the tissue under consideration. In particular, SERMs at the level of bone tissue behave as agonists of ERs but, as they do not result in the occurrence of estrogen side effects, they are widely used in the therapy of post-menopausal OP. This review provides a brief summary of the characteristics of SERMs employed in the treatment of post-menopausal OP.

Clinical Efficacy and Safety Evaluation of Calcitriol Combined with Bisphosphonates in the Therapy of Postmenopausal Osteoporosis: Based on a Retrospective Cohort Study.

A retrospective cohort study to explore the clinical efficacy and safety evaluation of calcitriol combined with bisphosphonates in the therapy of postmenopausal osteoporosis is conducted. The postmenopausal osteoporosis sufferers admitted to our hospital from January 2020 to June 2021 are retrospectively collected and divided into a contrast set and a study set, with 60 cases in each set. For the contrast set, all sufferers are treated with bisphosphonates. For the study set, on the basis of the therapy drugs in the contrast set, they are treated with calcitriol capsules. Firstly, the curative effects, bone mineral density standards, and bone metabolism standards of the two sets are contrasted; then, the lumbar spine bone mineral density, VAS score, and quality of life between the two sets of sufferers before therapy and 1 year after therapy are contrasted, and the correlation between bone mineral density and VAS and quality of life of the sufferers is analyzed. Lastly, the readmission situation between the two sets at one year is contrasted. The experimental results show that for postmenopausal women with osteoporosis, calcitriol combined with bisphosphonate therapy can notoriously enhance the clinical therapy effect of sufferers, with low adverse reactions, and can effectively enhance the bone mineral density and bone density of sufferers.

Trabecular bone microcrack accumulation in patients treated with bisphosphonates for durations up to 16 years.

This study quantified the length, number, and density of microcracks in bone from patients treated with bisphosphonates as a function of duration. Anterior iliac crest bone samples from 51 osteoporotic Caucasian females continuously treated with oral bisphosphonates for 1-16 years were obtained by bone biopsy. Samples were histologically processed and analyzed for bone area, microcrack number, and microcrack length. The analyses used statistical modeling and considered patient age, bone mineral density, bone volume/total volume, trabecular thickness, and bone turnover as potential covariates. Microcrack density (number of microcracks/total examined bone area) was linearly related (p = 0.018) to bisphosphonate treatment duration. None of the analyzed covariates contributed significantly to the observed relationship between microcrack density and bisphosphonate treatment duration. Observed increases in microcrack density with increasing bisphosphonate treatment duration is important because increasing levels of microcracks may not only affect bone remodeling but also reduce elastic modulus and are suspected to adversely affect other mechanical properties that may influence fracture risk. The present findings add to our prior results showing changes in bone material properties and modulus with bisphosphonate treatment duration and thereby provide a more comprehensive assessment of the relationship between bisphosphonate treatment duration and bone quality. Statement of Clinical Significance: The present findings provide information guiding clinical use of oral bisphosphonates for post-menopausal osteoporosis therapy.

Granular PEG hydrogels mediate osteoporotic MSC clustering via N-cadherin influencing the pro-resorptive bias of their secretory profile

Postmenopausal osteoporosis results from a pro-resorptive bone environment, which decreases bone mineral density causing increased fracture risk. Bone marrow derived mesenchymal stem/stromal cells (MSCs) secrete factors involved in bone homeostasis, but osteoporosis mediated changes to their secretions remain understudied. Herein, we examined the secretome of MSCs isolated from ovariectomized rats (OVX rMSCs), a model of post-menopausal osteoporosis, as a function of cell-cell interactions. Specifically, we controlled clustering of OVX and SHAM rMSCs by assembling them in granular hydrogels synthesized from poly(ethylene glycol) microgels with average diameters of ∼10, 100, and 200 µm. We directed both the sizes of rMSC clusters (single cells to ∼30 cells/cluster) and the percentages of cells within clusters (∼20–90%) by controlling the scaffold pore dimensions. Large clusters of OVX rMSCs had a pro-resorptive secretory profile, with increased concentrations of Activin A, CXCL1, CX3CL1, MCP-1, TIMP-1, and TNF-ɑ, compared to SHAM rMSCs. As this pro-resorptive bias was only observed in large cell clusters, we characterized the expression of several cadherins, mediators of cell-cell contacts. N-cadherin expression was elevated (∼4-fold) in OVX relative to SHAM rMSCs, in both cell clusters and single cells. Finally, TIMP-1 and MCP-1 secretion was only decreased in large cell clusters of OVX rMSCs when N-cadherin interactions were blocked, highlighting the dependence of OVX rMSC secretion of pro-resorptive cytokines on N-cadherin mediated cell-cell contacts. Further elucidation of the N-cadherin mediated osteoporotic MSC secretome may have implications for developing therapies for postmenopausal osteoporosis. Statement of significancePostmenopausal osteoporosis is a prevalent bone disorder that affects tens of millions of women worldwide. This disease is characterized by severe bone loss resulting from a pro-resorptive bone marrow environment, where the rates of bone resorption outpace the rates of bone deposition. The paracrine factors secreted by bone marrow MSCs can influence cell types responsible for bone homeostasis, but the osteoporosis-mediated changes to MSC secretory properties remains understudied. In this study, we used PEG-based porous granular scaffolds to study the influence of cell clustering on the secretory properties of osteoporotic MSCs. We observed increased secretion of several pro-resorptive factors by osteoporotic MSCs in large clusters. Further, we explored the dependence of this altered secretion profile on N-cadherin mediated cell-cell contacts.

Diagnosis and therapy of postmenopausal osteoporosis in clinical practice

Diagnosis and therapy of postmenopausal osteoporosis in clinical practice

Mesenchymal stem cells prevent ovariectomy-induced osteoporosis formation in mice through intraosseous vascular remodeling

Mesenchymal stem cells (MSCs) can promote osteogenesis and are a promising therapy for postmenopausal osteoporosis. However, the relationship between improved intraosseous microcirculation and increased bone mass induced by MSCs in postmenopausal osteoporosis remains unclear. After the primary MSCs were characterized, they were transplanted into ovariectomized mice. MSCs transplantation enhanced the trabecular number, trabecular bone volume/total volume, and trabecular bone mineral density in ovariectomized mice. To determine the role of MSCs in vascular repair, mice were subjected to femoral artery ligation. Through laser speckle flowmetry, vascular perfusion and femoral trabecular bone and cortical bone analyses, we determined the effects of MSCs in promoting intraosseous angiogenesis and preventing osteoporosis in mice. MSCs effectively prevented postmenopausal osteoporosis development, which is associated with the involvement of MSCs in reestablishment of microcirculation within the skeleton.

Exploration of a transdermal nanoemulgel as an alternative therapy for postmenopausal osteoporosis

The study investigated the ability of a transdermal nanoemulgel formulation to enhance the bioavailability and anti-osteoporotic efficacy of raloxifene hydrochloride (RH) using recent techniques such as micro-CT, SEM-EDX analysis. The ex-vivo permeation, histopathology, SEM, DSC and CLSM studies were carried out to determine the mechanistics of permeation. The in-vivo pharmacokinetic and pharmacodynamic studies were performed after establishing osteoporosis model using ovariectomy surgery. The biocompatibility of the developed nanoemulgel was tested as per OECD TG 439 protocol. The permeation of RH enhanced by 13 fold compared to plain drug gel. DSC and SEM examination showed change in microstructure of the skin which is the foundation for improved permeation. The pharmacokinetic study suggested 26 fold improved bioavailability of RH compared to per-oral marketed treatment. The micro-CT study demonstrated 202% enhanced bone mineral density. Improved pharmacokinetic and pharmacodynamic performance supported our claim of a successful delivery system. Our formulation is proposed to be safe, patient compliant and therapeutically effective alternative to the available marketed product.

New therapeutic options for bone diseases.

In recent years, new treatment options for both common and rare bone diseases have become available. The sclerostin antibody romosozumab is the most recently approved drug for the therapy of postmenopausal osteoporosis. Its anabolic capacity makes it apromising treatment option for severe osteoporosis. Other sclerostin antibodies for the treatment of rare bone diseases such as osteogenesis imperfecta are currently being investigated. For rare bone diseases such as X‑linked hypophosphatemia (XLH) and hypophosphatasia (HPP), specific therapies are now also available, showing promising data in children and adults with asevere disease course. However, long-term data are needed to assess asustained benefit for patients.

LncRNA LOXL1-AS1 controls osteogenic and adipocytic differentiation of bone marrow mesenchymal stem cells in postmenopausal osteoporosis through regulating the miR-196a-5p/Hmga2 axis.

Exploring molecular mechanisms of human bone marrow mesenchymal stem cells (hBMMSCs) differentiation, a crucial step for bone formation, is a new direction for treating postmenopausal osteoporosis. LncRNAs are involved in lots of biological processes including hBMMSCs differentiation. The present study aimed to explore the effect of LOXL1-AS1 on hBMMSCs differentiation. We examined the expression levels of LOXL1-AS1, miR-196a-5p and Hmga2 in peripheral blood from postmenopausal osteoporosis patients by RT-qPCR, and detected their changes during the osteogenic differentiation of hBMMSCs by RT-qPCR. RT-qPCR and western blot measured the level of biomarkers of bone formation and osteogenic differentiation (osteopontin, OPN; Alkaline phosphatase, ALP; Runt-related transcription factor-2, Runx-2). The effects of LOXL1-AS1 on the osteogenic and adipocytic differentiation of hBMMSCs were, respectively, determined by ALP, ARS staining assays and oil red O staining assay. The abnormal high expression of LOXL1-AS1 was found in patients. LOXL1-AS1 expression showed a gradual decrease during the osteogenic differentiation of hBMMSCs. However, LOXL1-AS1 overexpression inhibited the hBMMSCs osteogenic differentiation but promoted adipocytic differentiation. Furthermore, LOXL1-AS1 was identified to be a sponge of miR-196a-5p and Hmga2 as a target gene of miR-196a-5p. Besides, LOXL1-AS1 sponged miR-196a-5p to mediate Hmga2 expression, which played contrary effects on regulating osteogenic and adipocytic differentiation of hBMMSCs. Moreover, LOXL1-AS1/miR-196a-5p/Hmga2 axis regulated hBMMSCs differentiation through controlling C/EBPβ-mediated PPARγ expression. These findings facilitate understanding the molecular mechanism of hBMMSCs differentiation and bring up a novel sight for postmenopausal osteoporosis therapy.