miR-107 reverses the multidrug resistance of gastric cancer by targeting the CGA/EGFR/GATA2 positive feedback circuit.

Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.

Integrated metabolomics and proteomics analysis to understand muscle atrophy resistance in hibernating Spermophilus dauricus.

Hibernating Spermophilus dauricus experiences minor muscle atrophy, which is an attractive anti-disuse muscle atrophy model. Integrated metabolomics and proteomics analysis was performed on the hibernating S. dauricus during the pre-hibernation (PRE) stage, torpor (TOR) stage, interbout arousal (IBA) stage, and post-hibernation (POST) stage. Time course stage transition-based (TOR vs. PRE, IBA vs. TOR, POST vs. IBA) differential expression analysis was performed based on the R limma package. A total of 14 co-differential metabolites were detected. Among these, l-cystathionine, l-proline, ketoleucine, serine, and 1-Hydroxy-3,6,7-Trimethoxy-2, 8-Diprenylxanthone demonstrated the highest levels in the TOR stage; Beta-Nicotinamide adenine dinucleotide, Dihydrozeatin, Pannaric acid, and Propionylcarnitine demonstrated the highest levels in the IBA stage; Adrenosterone, PS (18:0/14,15-EpETE), S-Carboxymethylcysteine, TxB2, and 3-Phenoxybenzylalcohol demonstrated the highest levels in the POST stage. Kyoto Encyclopedia of Genes and Genomes pathways annotation analysis indicated that biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism were co-differential metabolism pathways during the different stages of hibernation. The stage-specific metabolism processes and integrated enzyme-centered metabolism networks in the different stages were also deciphered. Overall, our findings suggest that (1) the periodic change of proline, ketoleucine, and serine contributes to the hindlimb lean tissue preservation; and (2) key metabolites related to the biosynthesis of amino acids, ATP-binding cassette transporters, and cysteine and methionine metabolism may be associated with muscle atrophy resistance. In conclusion, our co-differential metabolites, co-differential metabolism pathways, stage-specific metabolism pathways, and integrated enzyme-centered metabolism networks are informative for biologists to generate hypotheses for functional analyses to perturb disuse-induced muscle atrophy.

Recent Progress in the Research on RNA-Binding Proteins in Bone Development and Diseases.

RNA-binding proteins (RBPs), which regulate gene expression through post-transcriptional modifications of RNAs, play a role in diverse biological processes that include bone cell development and bone tissue formation. RBP dysregulation may result in aberrant bone homeostasis and contribute to various bone diseases. The function of RBPs in bone physiology and pathophysiology and the underlying molecular mechanisms have been extensively studied in recent years. This article provides a review of such studies, highlighting the potential of RBPs as pivotal targets for therapeutic intervention.

Transcriptomic and proteomic time-course analyses based on Metascape reveal mechanisms against muscle atrophy in hibernating Spermophilus dauricus.

Hibernating Spermophilus dauricus is resistant to muscle atrophy. Comprehensive transcriptome and proteome time-course analyses based on Metascape can further reveal the underlying processes (pre-hibernation stage, PRE; torpor stage, TOR; interbout arousal stage, IBA; and post-hibernation stage, POST). Transcriptome analysis showed that the cellular responses to growth factor stimulus and discrete oxygen levels continuously changed during hibernation. Proteomic analysis showed that neutrophil degranulation, sulfur compound metabolic process, and generation of precursor metabolites and energy continuously changed during hibernation. Molecular complex detection (MCODE) analysis in both transcriptome and proteome indicated that smooth muscle contraction was involved in the POST versus IBA stage, and peroxisome proliferator-activated receptor delta (Ppard), Myc proto-oncogene (Myc), Sp1 transcription factor (Sp1), and nuclear factor Kappa B subunit 1 (NFκB1) are the common TFs during the hibernation process. Integrated transcriptome and proteome analyses found 18 molecules in the TOR versus PRE stage, 1 molecule in the IBA versus TOR stage, and 16 molecules in the POST versus IBA stage. Among these molecules, carnitine palmitoyltransferase 1A (Cpt1a), SET and MYND domain containing 2 (Smyd2), four and a half LIM domains 1(Fhl1), reactive oxygen species modulator 1 (Romo1), and translocase of the inner mitochondrial membrane 50 (Timm50) were testified by Western blot. In conclusion, novel muscle atrophy resistance mechanisms can be deciphered by time-course transcriptome and proteome analyses based on Metascape.

Macrophage-Targeted Dextran Sulfate-Dexamethasone Conjugate Micelles for Effective Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic immune disease that causes joint affection and even disability. Activated macrophages play an important role in the pathogenesis and progression of RA by producing pro-inflammatory factors. The use of dexamethasone (DXM) is effective in relieving the intractable pain and inflammatory progression of RA. However, long-term use of DXM is strongly associated with increased rates of diabetes, osteoporosis, bone fractures, and mortality, which hinders its clinical use. In this study, the dextran sulfate-cisaconitic anhydride-dexamethasone (DXM@DS-cad-DXM) micelles were prepared to treat RA by selectively recognizing scavenger receptor (SR) on the activated macrophages. The potent targeting property of DXM@DS-cad-DXM micelles to SR was by fluorescence microscope. Additionally, the effective accumulation and powerful anti-inflammatory activity of DXM@DS-cad-DXM micelles were observed in the inflamed joints of adjuvant-induced arthritis (AIA) rats after intravenous administration. Overall, DXM@DS-cad-DXM micelles are a potentially effective nanomedicine for targeted therapy of RA.

Comprehensive ceRNA network for MACF1 regulates osteoblast proliferation.

BACKGROUND: Previous studies have shown that microtubule actin crosslinking factor 1 (MACF1) can regulate osteoblast proliferation and differentiation through non-coding RNA (ncRNA) in bone-forming osteoblasts. However, the role of MACF1 in targeting the competing endogenous RNA (ceRNA) network to regulate osteoblast differentiation remains poorly understood. Here, we profiled messenger RNA (mRNA), microRNA (miRNA), and long ncRNA (lncRNA) expression in MACF1 knockdown MC3TC­E1 pre­osteoblast cells. RESULTS: In total, 547 lncRNAs, 107 miRNAs, and 376 mRNAs were differentially expressed. Significantly altered lncRNAs, miRNAs, and mRNAs were primarily found on chromosome 2. A lncRNA-miRNA-mRNA network was constructed using a bioinformatics computational approach. The network indicated that mir-7063 and mir-7646 were the most potent ncRNA regulators and mef2c was the most potent target gene. Pathway enrichment analysis showed that the fluid shear stress and atherosclerosis, p53 signaling, and focal adhesion pathways were highly enriched and contributed to osteoblast proliferation. Importantly, the fluid shear stress and atherosclerosis pathway was co-regulated by lncRNAs and miRNAs. In this pathway, Dusp1 was regulated by AK079370, while Arhgef2 was regulated by mir-5101. Furthermore, Map3k5 was regulated by AK154638 and mir-466q simultaneously. AK003142 and mir-3082-5p as well as Ak141402 and mir-446 m-3p were identified as interacting pairs that regulate target genes. CONCLUSION: This study revealed the global expression profile of ceRNAs involved in the differentiation of MC3TC­E1 osteoblasts induced by MACF1 deletion. These results indicate that loss of MACF1 activates a comprehensive ceRNA network to regulate osteoblast proliferation.

The role of protein glycosylation in muscle diseases.

INTRODUCTION: As a post-translational modification, glycosylation plays vital role in regulating the folding and function of proteins necessary for many biological processes. Unlike glycation, glycosylation is an enzymatic process; glycosyltransferases transfer sugars to proteins, forming glycosidic bonds with amino acid residues on proteins. Changes that interfere with the enzymatic reaction and result in abnormal glycosylation can spatio-temporally affect the balance of glycosylation, leading to disease states. Muscle diseases have been associated with dysfunctional protein glycosylation, and many studies have focused on the pathophysiology underlying this association. This review aims to summarize the research progress on protein glycosylation in the pathogenesis of muscle diseases and provides new insight into the muscle research field. METHODS: Literatures were reviewed comparatively and data were organized to find information about protein glycosylation and its role in muscle disease. RESULTS: Protein glycosylation modification is closely related to the occurrence of muscle diseases. α-DG is a key protein in the study of inherited muscle diseases and has a wide range of glycosylation, including O-linked glycosylation and N-linked glycosylation. Besides, O-GlcNAc glycosylation is an important mechanism of protein glycosylation, helping maintaining the structure and function of skeletal muscle and participating in multiple biological processes. Protein glycosylation is also connected to muscle disease and neurodegenerative diseases, especially Alzheimer's disease. CONCLUSIONS: Taken together, better understanding of protein glycosylation and its implication in muscle disease would help provide new perspectives in the prevention and treatment measures for human muscle diseases.

Toxicity prediction of 1,2,4-triazoles compounds by QSTR and interspecies QSTTR models.

1,2,4-triazole derivatives exhibit various biological activities, including antibacterial and antifungal properties. On the other hand, these chemicals may have unique cumulative and harmful effects on living organisms. The goal of this work is to use quantitative structure-toxicity relationship (QSTR) and interspecies quantitative toxicity-toxicity relationship (iQSTTR) models to predict the acute toxicity of 1,2,4-triazole derivatives. The QSTR models were generated by multiple linear regression (MLR) following the OECD recommendations for QSAR model development and validation. The iQSTTR models were constructed using data on acute oral toxicity in rats and mice, as well as the 2D descriptor. The application domain (AD) analysis was used to identify model outliers and determine if the forecast was credible. Six QSTR models were successfully constructed in rats and mice using various delivery methods, and the scatter plots demonstrated excellent consistency across training and test sets. According to external and internal validation criteria, all six QSTR models may be broadly accepted; however, the orally administered mice model was the optimum one among the six species. Several chemicals with leverage values above the requirements were identified as response or structural outliers in the training sets for six QSTR and two iQSTTR models. All outliers, however, fell slightly outside the threshold or had low prediction errors, which may have had little impact on the capacity to forecast and were therefore preserved in the final models. In fact, neither the QSTR nor the iQSTTR test sets contained any response outliers. Additionally, all external and internal validation results for the iQSTTR models were approved, with the iQSTTR models outperforming the comparable QSTR models, which are deemed more dependable. The QSTR and iQSTTR models performed well in predicting toxicity using test sets, which would be beneficial in evaluating and synthesizing newly discovered 1,2,4-triazoles derivatives with low toxicity and environmental hazard.

A rapid degradation of calponin 2 is required for cytokinesis.

Calponin 2 is an actin cytoskeleton-associated protein and plays a role in regulating cell motility-related functions such as phagocytosis, migration, and division. We previously reported that overexpression of calponin 2 inhibits the rate of cell proliferation. To investigate the underlying mechanism, our present study found that the levels of endogenous calponin 2 in NIH3T3 and HEK293 cells rapidly decreased before cell division characterized by an absence at the actin contractile ring. In cells lacking endogenous calponin 2, transfective expression of GFP-fusion calponin 2 inhibited cell proliferation similar to that of nonfusion calponin 2. Fluorescent imaging studies of mitotic cells indicated that a proper level of calponin 2 expression and effective degradation during cytokinesis are necessary for normal cell division. Computer-assisted dynamic image analysis of dividing cells revealed that overexpression of calponin 2 significantly affects motility and shape behaviors of cells only on the interval from the start of anaphase to the start of cytokinesis, i.e., the pre-cytokinesis phase, but not on the interval from the start of cytokinesis to 50% completion of cytokinesis. The pre-cytokinesis degradation of calponin 2 was attenuated by MG132 inhibition of the ubiquitin proteasome and inhibitor of protein kinase C (PKC), suggesting that PKC phosphorylation-triggered degradation of calponin 2 could determine the rate of cytokinesis. The novel role of calponin 2 in regulating the rate of cytokinesis may be targeted for therapeutic applications such as in an inhibition of malignant tumor growth.

MACF1 alleviates aging-related osteoporosis via HES1.

Ageing-related osteoporosis is becoming an emerging threat to human health along with the ageing of human population. The decreased rate of osteogenic differentiation and bone formation is the major cause of ageing-related osteoporosis. Microtubule actin cross-linking factor 1 (MACF1) is an important cytoskeletal factor that promotes osteogenic differentiation and bone formation. However, the relationship between MACF1 expression and ageing-related osteoporosis remains unclear. This study has investigated the expression pattern of MACF1 in bone tissues of ageing-related osteoporosis patients and ageing mice. The study has further elucidated the mechanism of MACF1 promoting bone formation by inhibiting HES1 expression and activity. Moreover, the therapeutic effect of MACF1 on ageing-related osteoporosis and post-menopausal osteoporosis was evaluated through in situ injection of the MACF1 overexpression plasmid. The study supplemented the molecular mechanisms between ageing and bone formation, and provided novel targets and potential therapeutic strategy for ageing-related osteoporosis.

Landscape of immune cell infiltration in clear cell renal cell carcinoma to aid immunotherapy.

The tumor microenvironment, comprised of tumor cells and tumor-infiltrating immune cells, is closely associated with the clinical outcome of clear cell renal cell carcinoma (ccRCC) patients. However, the landscape of immune infiltration in ccRCC has not been fully elucidated. Herein, we applied multiple computational methods and various datasets to reveal the immune infiltrative landscape of ccRCC patients. The tumor immune infiltration (TII) levels of 525 ccRCC patients using a single-sample gene were examined and further categorized into immune infiltration subgroups. The TII score was characterized by distinct clinical traits and showed a significant divergence based on gender, grade, and stage. A high TII score was associated with the ERBB signaling pathway, the TGF-ß signaling pathway, and the MTOR signaling pathway, as well as a better prognosis. Furthermore, patients with high TII scores exhibited greater sensitivity to pazopanib. The low TII score was characterized by a high immune infiltration level of CD8+ T cells, T follicular helper cells, and regulatory T cells (Tregs). Moreover, the immune check point genes, including CTLA-4, LAG3, PD-1, and IDO1, presented a high expression level in the low TII score group. Patients in the high TII score group demonstrated significant therapeutic advantages and clinical benefits. The findings in this study have the potential to assist in the strategic design of immunotherapeutic treatments for ccRCC.

Long noncoding RNA AK039312 and AK079370 inhibits bone formation via miR-199b-5p.

Osteoporosis caused by aging and menopause had become an emerging threat to human health. The reduction of osteoblast differentiation has been considered to be an essential cause of osteoporosis. Osteoblast differentiation could be regulated by LncRNAs, and increasing evidences have proved that LncRNAs may be adopted as potential therapeutic targets for osteoporosis. However, reports on rescue effects of LncRNAs in vivo are relatively limited. In this study, two LncRNAs (AK039312 and AK079370) were screened as osteogenic related LncRNAs. Both AK039312 and AK079370 could inhibit osteoblast differentiation and bone formation through suppressing osteogenic transcription factors. This inhibitory effect was achieved via binding and sequestering miR-199b-5p, and enhanced GSK-3ß which further inhibited wnt/ß-catenin pathway. Moreover, the siRNAs of AK039312 and AK079370 significantly alleviated postmenopausal osteoporosis, and the combination of si-AK039312 and si-AK079370 was more efficient than applying one si-LncRNA alone. This study has provided new insights for the therapy of osteoporosis.

Cytotoxicity and inflammatory effects in human bronchial epithelial cells induced by polycyclic aromatic hydrocarbons mixture.

Polycyclic aromatic hydrocarbons (PAHs) are the most common contaminants in the air pollutants. Inhalation exposure to PAHs could increase the risk of respiratory disease, cardiovascular disease and even cancer. However, the biotoxicity of multi-component PAHs from atmospheric pollutants has been poorly studies. The main topic of this study was to investigate the PAHs mixture, which derived from atmospheric pollutants, induced toxic effects and inflammatory effects on human bronchial epithelial cells in vitro. The results showed that PAHs mixture could decrease the cell viability, increase the apoptosis rate, and induce cell cycle arrest at S-phase. Furthermore, the expression of inflammatory factors IL-1ß and IL-6 were increased and NF-κB signaling pathway was activated in PAHs mixture-treated cells. The findings of this study indicate that PAHs mixture-induced cytotoxicity and inflammation may be related to intracellular ROS generation and to the activated NF-κB signaling pathway.

NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves.

Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats' lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone.

Piezo channels are mechanosensitive ion channels located in the cell membrane and function as key cellular mechanotransducers for converting mechanical stimuli into electrochemical signals. Emerged as key molecular detectors of mechanical forces, Piezo channels' functions in bone have attracted more and more attention. Here, we summarize the current knowledge of Piezo channels and review the research advances of Piezo channels' function in bone by highlighting Piezo1's role in bone cells, including osteocyte, bone marrow mesenchymal stem cell (BM-MSC), osteoblast, osteoclast, and chondrocyte. Moreover, the role of Piezo channels in bone diseases is summarized.

Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway.

Microtubule actin cross-linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3-E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast-specific Osterix (Osx) promoter-driven Macf1 conditional knockout mice (Macf1f/f Osx-Cre). The Macf1f/f Osx-Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1f/f Osx-Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1f/f Osx-Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1f/f Osx-Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease.

Role of cancer stem cells in the development of giant cell tumor of bone.

The primary bone tumor is usually observed in adolescence age group which has been shown to be part of nearly 20% of the sarcomas known today. Giant cell tumor of bone (GCTB) can be benign as well as malignant tumor which exhibits localized dynamism and is usually associated with the end point of a long bone. Giant cell tumor (GCT) involves mononuclear stromal cells which proliferate at a high rate, multinucleated giant cells and stromal cells are equally present in this type of tumor. Cancer stem cells (CSCs) have been confirmed to play a potential role in the development of GCT. Cancer stem cell-based microRNAs have been shown to contribute to a greater extent in giant cell tumor of bone. CSCs and microRNAs present in the tumors specifically are a great concern today which need in-depth knowledge as well as advanced techniques to treat the bone cancer effectively. In this review, we attempted to summarize the role played by cancer stem cells involving certain important molecules/factors such as; Mesenchymal Stem Cells (MSCs), miRNAs and signaling mechanism such as; mTOR/PI3K-AKT, towards the formation of giant cell tumor of bone, in order to get an insight regarding various effective strategies and research advancements to obtain adequate knowledge related to CSCs which may help to focus on highly effective treatment procedures for bone tumors.

IoT PCR for pandemic disease detection and its spread monitoring.

During infectious disease outbreaks, the centers for disease control need to monitor particular areas. Considerable effort has been invested in the development of portable, user-friendly, and cost-effective systems for point-of-care (POC) diagnostics, which could also create an Internet of Things (IoT) for healthcare via a global network. However, at present IoT based on a functional POC instrument is not available. Here we show a fast, user-friendly, and affordable IoT system based on a miniaturized polymerase chain reaction device. We demonstrated the system's capability by amplification of complementary deoxyribonucleic acid (cDNA) of the dengue fever virus. The resulting data were then automatically uploaded via a Bluetooth interface to an Android-based smartphone and then wirelessly sent to a global network, instantly making the test results available anywhere in the world. The IoT system presented here could become an essential tool for healthcare centers to tackle infectious disease outbreaks identified either by DNA or ribonucleic acid.

The Role of MicroRNAs in Bone Metabolism and Disease.

Bone metabolism is an intricate process involving various bone cells, signaling pathways, cytokines, hormones, growth factors, etc., and the slightest deviation can result in various bone disorders including osteoporosis, arthropathy, and avascular necrosis of femoral head. Osteoporosis is one of the most prevalent disorders affecting the skeleton, which is characterized by low bone mass and bone mineral density caused by the disruption in the balanced process of bone formation and bone resorption. The current pharmaceutical treatments such as bisphosphonates, selective estrogen receptor modulator, calcitonin, teriparatide, etc., could decrease the risk of fractures but have side-effects that have limited their long term applications. MicroRNAs (miRNAs) are one of many non-coding RNAs. These are single-stranded with a length of 19-25 nucleotides and can influence various cellular processes and play an important role in various diseases. Therefore, in this article, we review the different functions of different miRNA in bone metabolism and osteoporosis to understand their mechanism of action for the development of possible therapeutics.

Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells.

Senile osteoporosis has become a worldwide bone disease with the aging of the world population. It increases the risk of bone fracture and seriously affects human health. Unlike postmenopausal osteoporosis which is linked to menopause in women, senile osteoporosis is due to aging, hence, affecting both men and women. It is commonly found in people with more than their 70s. Evidence has shown that with age increase, bone marrow stromal cells (BMSCs) differentiate into more adipocytes rather than osteoblasts and undergo senescence, which leads to decreased bone formation and contributes to senile osteoporosis. Therefore, it is necessary to uncover the molecular mechanisms underlying the functional changes of BMSCs. It will benefit not only for understanding the senile osteoporosis development, but also for finding new therapies to treat senile osteoporosis. Here, we review the recent advances of the functional alterations of BMSCs and the related mechanisms during senile osteoporosis development. Moreover, the treatment of senile osteoporosis by aiming at BMSCs is introduced.