Exosomes derived from BMSCs in osteogenic differentiation promote type H blood vessel angiogenesis through miR-150-5p mediated metabolic reprogramming of endothelial cells.

Osteogenesis is tightly coupled with angiogenesis spatiotemporally. Previous studies have demonstrated that type H blood vessel formed by endothelial cells with high expression of CD31 and Emcn (CD31hi Emcnhi ECs) play a crucial role in bone regeneration. The mechanism of the molecular communication around CD31hi Emcnhi ECs and bone mesenchymal stem cells (BMSCs) in the osteogenic microenvironment is unclear. This study indicates that exosomes from bone mesenchymal stem cells with 7 days osteogenic differentiation (7D-BMSCs-exo) may promote CD31hi Emcnhi ECs angiogenesis, which was verified by tube formation assay, qRT-PCR, Western blot, immunofluorescence staining and µCT assays etc. in vitro and in vivo. Furthermore, by exosomal miRNA microarray and WGCNA assays, we identified downregulated miR-150-5p as the most relative hub gene coupling osteogenic differentiation and type H blood vessel angiogenesis. With bioinformatics assays, dual luciferase reporter experiments, qRT-PCR and Western blot assays, SOX2(SRY-Box Transcription Factor 2) was confirmed as a novel downstream target gene of miR-150-5p in exosomes, which might be a pivotal mechanism regulating CD31hi Emcnhi ECs formation. Additionally, JC-1 immunofluorescence staining, Western blot and seahorse assay results showed that the overexpression of SOX2 could shift metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis to enhance the CD31hi Emcnhi ECs formation. The PI3k/Akt signaling pathway might play a key role in this process. In summary, BMSCs in osteogenic differentiation might secrete exosomes with low miR-150-5p expression to induce type H blood vessel formation by mediating SOX2 overexpression in ECs. These findings might reveal a molecular mechanism of osteogenesis coupled with type H blood vessel angiogenesis in the osteogenic microenvironment and provide a new therapeutic target or cell-free remedy for osteogenesis impaired diseases.

Nuciferine prevents bone loss by disrupting multinucleated osteoclast formation and promoting type H vessel formation.

Recently, type H vessels were reported to couple angiogenesis and osteogenesis during osteoclastogenesis, and tartrate-resistant acid phosphatase (Trap)+ preosteoclasts were found to secrete increased PDGF-BB to promote type H vessel formation. Therefore, utilization of type H vessels may be a strategy to treat diseases involving bone loss. In the present study, we found that nuciferine, a natural bioactive compound, has various effects, including inhibiting osteoclastogenesis and promoting type H vessel formation. Nuciferine inhibited osteoclastogenesis and bone resorption but increased the relative number of Trap+ preosteoclasts. Nuciferine restrained the expression of osteoclast-specific genes and proteins, promoted PDGF-BB production and potentiated related angiogenic activities by inhibiting the MAPK and NF-κB signaling pathways in vitro. We confirmed the bone-protective effects of nuciferine in ovariectomized mice and found that nuciferine treatment increased the PDGF-BB concentration and the number of type H vessels in the femur. In conclusion, our results demonstrated that nuciferine can decrease multinucleated osteoclast formation and promote type H vessel formation through preservation of Trap+ preosteoclasts via inhibition of the MAPK and NF-κB signaling pathways and may be an excellent agent for the treatment of diseases involving bone loss.

Methylation-mediated down-regulation of microRNA-497-195 cluster confers osteogenic differentiation in ossification of the posterior longitudinal ligament of the spine via ADORA2A.

Aberrant expression of microRNAs (miRNAs) has been associated with spinal ossification of the posterior longitudinal ligament (OPLL). Our initial bioinformatic analysis identified differentially expressed ADORA2A in OPLL and its regulatory miRNAs miR-497 and miR-195. Hence, this study was conducted to clarify the functional relevance of miR-497-195 cluster in OPLL, which may implicate in Adenosine A2A (ADORA2A). PLL tissues were collected from OPLL and non-OPLL patients, followed by quantification of miR-497, miR-195 and ADORA2A expression. The expression of miR-497, miR-195 and/or ADORA2A was altered in posterior longitudinal ligament (PLL) cells, which then were stimulated with cyclic mechanical stress (CMS). We validated that ADORA2A was expressed highly, while miR-497 and miR-195 were down-regulated in PLL tissues of OPLL patients. miR-195 and miR-497 expression in CMS-treated PLL cells was restored by a demethylation reagent 5-aza-2'-deoxycytidine (AZA). Moreover, expression of miR-195 and miR-497 was decreased by promoting promoter CpG island methylation. ADORA2A was verified as the target of miR-195 and miR-497. Overexpression of miR-195 and miR-497 diminished expression of osteogenic factors in PLL cells by inactivating the cAMP/PKA signaling pathway via down-regulation of ADORA2A. Collectively, miR-497-195 cluster augments osteogenic differentiation of PLL cells by inhibiting ADORA2A-dependent cAMP/PKA signaling pathway.

Synovial fibroblast-targeting liposomes encapsulating an NF-κB-blocking peptide ameliorates zymosan-induced synovial inflammation.

Synovial fibroblasts (SFs) play a crucial role in the inflammatory process of rheumatoid arthritis (RA). The highly activated NF-κB signal in SFs is responsible for most of the synovial inflammation associated with this disease. In this study, we have developed an SF-targeting liposomal system that encapsulates the NF-κB-blocking peptide (NBD peptide) HAP-lipo/NBD. HAP-lipo/NBDs demonstrated efficient SF-specific targeting in vitro and in vivo. Our study also showed a significant inhibitory effect of HAP-lipo/NBD on NF-κB activation, inflammatory cytokine release and SF migration capability after zymosan stimulation. Furthermore, the systemic administration of HAP-lipo/NBDs significantly inhibited synovial inflammation and improved the pathological scores of arthritis induced by zymosan. Thus, these results suggest that an SF-targeting NF-κB-blocking strategy is a potential approach for the development of alternative, targeted anti-RA therapies.

Identification and validation of hub genes and potential drugs involved in osteoarthritis through bioinformatics analysis.

Purpose: Osteoarthritis (OA) is a common degenerative disease, which still lacks specific therapeutic drugs. Synovitis is one of the most important pathological process in OA. Therefore, we aim to identify and analyze the hub genes and their related networks of OA synovium with bioinformatics tools to provide theoretical basis for potential drugs. Materials and methods: Two datasets were obtained from GEO. DEGs and hub genes of OA synovial tissue were screened through Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment as well as protein-protein interaction (PPI) network analysis. Subsequently, the correlation between expression of hub genes and ferroptosis or pyroptosis was analyzed. CeRNA regulatory network was constructed after predicting the upstream miRNAs and lncRNAs. The validation of hub genes was undertook through RT-qPCR and ELISA. Finally, potential drugs targeting pathways and hub genes were identified, followed by the validation of the effect of two potential drugs on OA. Results: A total of 161 commom DEGs were obtained, of which 8 genes were finally identified as hub genes through GO and KEGG enrichment analysis as well as PPI network analysis. Eight genes related to ferroptosis and pyroptosis respectively were significantly correlated to the expression of hub genes. 24 miRNAs and 69 lncRNAs were identified to construct the ceRNA regulatory network. The validation of EGR1, JUN, MYC, FOSL1, and FOSL2 met the trend of bioinformatics analysis. Etanercept and Iguratimod reduced the secretion of MMP-13 and ADAMTS5 of fibroblast-like synoviocyte. Conclusion: EGR1, JUN, MYC, FOSL1, and FOSL2 were identified as hub genes in the development of OA after series of bioinformatics analysis and validation. Etanercept and Iguratimod seemed to have opportunities to be novel drugs for OA.

Ferroptosis Plays a Role in Human Chondrocyte of Osteoarthritis Induced by IL-1ß In Vitro.

OBJECTIVE: Osteoarthritis (OA) is a common disease with complex and unclear pathogenesis. Ferroptosis is a new cell death mode, which is proved to be involved in different kinds of disease. We hypothesized that ferroptosis contributes to the progress of human OA. DESIGN: Chondrocytes were extracted from waste cartilage of total knee arthroplasty, and stimulated with interleukin-1ß (IL-1ß). Then, we detected the morphology, proliferation, and viability, and levels of Fe3+, glutathione (GSH), reactive oxygen species (ROS), malondialdehyde (MDA), and 5 proteins related to ferroptosis with or without intervention of ferrostatin-1 (Fer-1). In addition, we compared the effect of Fer-1 and liproxstatin-1 (Lip-1) on ferroptosis and the protection of chondrocytes by detecting several markers of both ferroptosis and OA. RESULTS: After stimulation of IL-1ß, there were significant changes on the shape of chondrocyte, with lower viability and proliferation. There was accumulation of intracellular Fe3+, GSH, ROS, and MDA, with the changes of expression of 5 ferroptosis-related proteins. With the contribution of Fer-1, results above were reversed. Moreover, there was no significant difference in GPX4 and ACSL4 between Fer-1 and Lip-1 group. However, the expression of COLX, ADAMTS5, and MMP-13 are lower after the treatment of Fer-1 compared with Lip-1. CONCLUSIONS: Ferroptosis plays an important role in human OA chondrocytes, which can be reversed by Fer-1, illustrating that inhibitor of ferroptosis may be a potential treatment of OA. Moreover, Lip-1 and Fer-1 can both alleviate the level of ferroptosis in OA chondrocytes, but Fer-1 had a more protective effect.

Bioinformatic Data Mining for Candidate Drugs Affecting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) in Cancer Patients.

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) leads to significant morbidity. Other coadministered drugs may modulate the risk for BRONJ. The present study aimed to leverage bioinformatic data mining to identify drugs that potentially modulate the risk of BRONJ in cancer. Methods: A GEO gene expression dataset of peripheral blood mononuclear cells related to BRONJ in multiple myeloma patients was downloaded, and differentially expressed genes (DEGs) in patients with BRONJ versus those without BRONJ were identified. A protein-protein interaction network of the DEGs was constructed using experimentally validated interactions in the STRING database. Overrepresented Gene Ontology (GO) molecular function terms and KEGG pathways in the network were analysed. Network topology was determined, and 'hub genes' with degree ≥2 in the network were identified. Known drug targets of the hub genes were mined from the 'drug gene interaction database' (DGIdb) and labelled as candidate drugs affecting the risk of BRONJ. Results: 751 annotated DEGs (log FC ≥ 1.5, p < 0.05) were obtained from the microarray gene expression dataset GSE7116. A PPI network with 633 nodes and 168 edges was constructed. Data mining for drugs interacting with 49 gene nodes was performed. 37 drug interactions were found for 9 of the hub genes including TBP, TAF1, PPP2CA, PRPF31, CASP8, UQCRB, ACTR2, CFLAR, and FAS. Interactions were found for several established and novel anticancer chemotherapeutic, kinase inhibitor, caspase inhibitor, antiangiogenic, and immunomodulatory agents. Aspirin, metformin, atrovastatin, thrombin, androgen and antiandrogen drugs, progesterone, Vitamin D, and Ginsengoside 20(S)-Protopanaxadiol were also documented. Conclusions: A bioinformatic data mining strategy identified several anticancer, immunomodulator, and other candidate drugs that may affect the risk of BRONJ in cancer patients.

Downregulated fat mass and obesity-associated protein inhibits bone resorption and osteoclastogenesis by nuclear factor-kappa B inactivation.

During osteoporosis, fat mass and obesity-associated protein (FTO) promotes the shift of bone marrow mesenchymal stem cells to adipocytes and represses osteoblast activity. However, the role and mechanisms of FTO on osteoclast formation and bone resorption remain unknown. In this study, we investigated the effect of FTO on RAW264.7 cells and bone marrow monocytes (BMMs)-derived osteoclasts in vitro and observed the influence of FTO on ovariectomized (OVX) mice model to mimic postmenopausal osteoporosis in vivo. Results found that FTO was up-regulated in BMMs from OVX mice. Double immunofluorescence assay showed co-localization of FTO with tartrate-resistant acid phosphatase (TRAP) in femurs of OVX mice. FTO overexpression enhanced TRAP-positive osteoclasts and F-actin ring formation in RAW264.7 cells upon RANKL stimulation. The expression of osteoclast differentiation-related genes, including nuclear factor of activated T cells c1 (NFATc1) and c-FOS, was upregulated in BMMs and RAW264.7 cells after FTO overexpression. FTO overexpression induced the phosphorylation and nuclear translocation of factor-kappa B (NF-κB) p65 in BMMs and RAW264.7 cells exposed to RANKL. ChIP and dual-luciferase assays revealed that FTO overexpression contributed to RANKL-induced binding of NF-κB to NFATc1 promoter. Rescue experiments suggested that FTO overexpression-mediated osteoclast differentiation was suppressed after intervention with a NF-κB inhibitor pyrrolidine dithiocarbamate. Further in vivo evidence revealed that FTO knockdown increased bone trabecula and bone mineral density, inhibited bone resorption and osteoclastogenesis in osteoporotic mice. Collectively, our research demonstrates that downregulated FTO inhibits bone resorption and osteoclastogenesis through NF-κB inactivation, which provides a novel reference for osteoporosis treatment.

Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors.

BACKGROUND: The SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system. METHODS: The Oncomine, Ualcan, Kaplan-Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD). RESULTS: In ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites. CONCLUSION: SMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.

A modular programmed biphasic dual-delivery system on 3D ceramic scaffolds for osteogenesis in vitro and in vivo.

Single-factor delivery is the most common characteristic of bone tissue engineering techniques. However, bone regeneration is a complex process requiring multiple factors and specialized release mechanisms. Therefore, the development of a dual-delivery system allowing for programmed release kinetics would be highly desirable. Improvement of the molarity and versatility of the delivery system has rarely been studied. Herein, we report the development of a novel, modular programmed biphasic dual-release system (SCB), carrying a BMP2 and an engineered collagen I-derived recognition motif (Stath-DGEA), with a self-remodification feature on hydroxyapatite (HA)-based materials. The SCB system was loaded onto an additive manufactured (AM) scaffold in order to evaluate its bifactor osteogenic potential and its biphasic release behavior. Further, the biomechanical properties of the scaffold were studied by using the fluid-structure interaction (FSI) method. Section fluorescent labeling revealed that the HA scaffold has a relatively higher density and efficiency. Additionally, the results of the release and inhibition experiment suggested that the SCB system could facilitate the sustained release of therapeutic levels of two factors during the initial stage of implantation, thereby exhibiting a rapid high-dose release pattern at a specific time point during the second stage. The FSI prediction model indicated that the scaffold provides an excellent biomimetic mechanical and fluid dynamic microenvironment to promote osteogenesis. Our results indicated that incorporation of BMP2 with Stath-DGEA in the biphasic SCB system could have a synergetic effect in promoting the adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro, under staged stimulations. Further, in vivo studies in both ectopic and orthotopic rat models showed that the SCB system loaded onto an AM scaffold could enhance osteointegration and osteoinduction throughout the osteogenic process. Thus, the novel synthetic SCB system described herein used on an AM scaffold provides a biomimetic extracellular environment that enhances bone regeneration and is a promising multifunctional, dual-release platform.

Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis.

Intestinal dysmotility is a frequent complication during sepsis and plays an important role in the development of secondary infections and multiple organ failure. However, the central mechanisms underlying this process have not been well elucidated. Currently, effective therapies are still lacking for the treatment of sepsis-induced intestinal dysmotility. In this study, we found that the activation of IL-17 signaling within the muscularis propria might be associated with dysmotility of the small intestine during polymicrobial sepsis. Furthermore, we demonstrated that targeting IL-17A partially rescued the motility of the small intestine and alleviated interstitial cells of Cajal (ICC) injury during sepsis. The blockade of IL-17A suppressed the dominant sepsis-induced infiltration of M1-polarized macrophages into the muscularis. Additionally, impaired ICC survival may be associated with the oxidative stress injury induced by dominant infiltration of M1-polarized macrophages. Our findings reveal the important role of the IL-17 signaling pathway in the small intestine during sepsis and provide clues for developing a novel therapeutic strategy for treating gastrointestinal dysmotility during sepsis.

A three-dimensional (3D) printed biomimetic hierarchical scaffold with a covalent modular release system for osteogenesis.

Hydroxyapatite (HA) ceramics are well known for their biocompatibility, bioactivity, and osteoconductive nature. However, limited hierarchical structure and lack of ease in modularity hinder the widespread application of conventional HA ceramics. By using three-dimensional printing (3DP) techniques with multiple materials, including HA, complex biological and mechanical architecture of natural organisms can be achieved through biomimetics. In this study, we designed an osteoid, biomimetic, hierarchical, porous HA ceramic 3D printed scaffold (3DPs). Further incorporation of a covalent, modular, controlled release system (CMR), based on Watson-Crick's complementary oligonucleotides, and was added to carry a bone morphogenetic protein-2 (BMP2) peptide. The choice of a HA biomimetic scaffold housing BMP2 protein fragments was selected to successfully promote osteogenesis both in vitro and in vivo. Scanning electron microscopy, micro-computed tomography analysis and computer fluid dynamics simulations of the 3DPs showed a uniform biomimetic hierarchical structure and an effective interior permeability. Active molecules were found bound with high stability and modular to the scaffold surface via the CMR system. After 7 days of incubation under physiological conditions, approximately 90% of active factors remained bound. Compared to control groups, the 3DPs-CMR-BMP2 group significantly enhanced cell proliferation and adhesion. Moreover, the 3DPs-CMR-BMP2 group exhibited more extensive and sustained osteogenic effects through upregulated expression of osteogenic factors and enhanced calcium deposition, as compared to study and control groups. Furthermore, ectopic osteogenesis and a critical calvarial defect model confirmed that the 3DPs-CMR-BMP2 group significantly promoted in vivo bone healing versus control. Thus, our results showed that biomimetic hierarchical 3DPs with a CMR system successfully promote cell proliferation, adhesion, differentiation and osteogenesis, on a continuous cycle. The biomimetic hierarchical 3DPs with a CMR system offers a promising multi-functional, bone substitute material for treatment of patients with bone defects.

Skeletal-related events and overall survival of patients with bone metastasis from nonsmall cell lung cancer - A retrospective analysis.

Because of improving treatments and survival, 40% to 58% of patients with bone metastases from nonsmall cell lung cancer (NSCLC) will suffer from at least one skeletal-related event (SRE), affecting their quality of life, but the natural history of SRE is poorly understood. The study aimed to examine the factors involved in SRE-free survival (SRS) and overall survival (OS) of patients with NSCLC and bone metastases.This was a retrospective study of 211 patients with bone metastasis from NSCLC and treated at the Tumor Hospital Affiliated to Harbin Medical University between January 2007 and January 2012. OS and SRS were evaluated by the Kaplan-Meier method. The factors associated with SRS and OS were examined using multivariate Cox analyses.The 1 year OS was 55.9% and the median OS was 30 months (range, 1-98 months). Multivariate analyses showed that clinical staging at initial diagnosis (P < .001) and SRE (P = .033) were independently associated with OS, and clinical staging at initial diagnosis (P = .009), bone pain (P = .008), primary tumor radiotherapy (P < .001), and chemotherapy (P = .031) were independently associated with SRS. Stage I, II, and III patients under biphosphonate therapy fared better than those without biphosphonate treatment, but there was no difference for stage IV patients.The identification of factors associated with OS and SRS of patients with NSCLC and bone metastases should provide new clues for a better management of these patients.

Sesamin inhibits IL-1ß-stimulated inflammatory response in human osteoarthritis chondrocytes by activating Nrf2 signaling pathway.

Sesamin, a bioactive component extracted from sesame, has been reported to exert anti-inflammatory and anti-oxidant effects. In this study, we evaluated the anti-inflammatory effects of sesamin on IL-1ß-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that sesamin treatment significantly inhibited PGE2 and NO production induced by IL-1ß. Sesamin inhibited MMP1, MMP3, and MMP13 production in IL-1ß-stimulated chondrocytes. Sesamin also inhibited IL-1ß-induced phosphorylation of NF-κB p65 and IκBα. Meanwhile, sesamin was found to up-regulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of sesamin. In conclusion, our results suggested that sesamin showed anti-inflammatory effects in IL-1ß-stimulated chondrocytes by activating Nrf2 signaling pathway.

Enhanced expression of neurotrophic factors in the injured spinal cord through vaccination with myelin basic protein-derived peptide pulsed dendritic cells.

STUDY DESIGN: Vaccination of spinal cord injury (SCI) mice with myelin basic protein-derived peptide (A91) pulsed dendritic cells (DC) to enhance brain-derived neurotrophic factor and neurotrophin-3 (NT-3) expression in injured spinal cord. OBJECTIVE: To investigate the effect of A91-pulsed DC (A91-DC) on expression of neurotrophic factor in injured spinal cord. SUMMARY OF BACKGROUND DATA: SCI leads to progressive secondary tissue degeneration, and no satisfactory treatment is currently available. Accumulating evidence indicates that administration of neurotrophic factors to injured spinal cord is partially successful at promoting nerve tissue repair. However, most of strategy can cause secondary injury and limiting their wide clinical application. METHODS: Proliferation of T cells and the capability of CD4 T cells to secret neurotrophic factors were first measured in vitro to demonstrate the stimulus action of the A91-DC. In SCI mice model, enzyme-linked immunosorbent assay and immunofluorescence was employed to investigate the brain-derived neurotrophic factor and NT-3 expression in injured spinal cord. Furthermore, the neuroprotective effect of A91-DC in injured spinal cord was examined through histology measurement. RESULTS: In this study, we demonstrated that A91-DC promoted the capability of T cells to secret neurotrophic factors and in the subacute phase of SCI. Moreover, vaccination with A91-DC enhanced the expression level of brain-derived neurotrophic factor and NT-3 and exerted neuroprotective effect in injured spinal cord. CONCLUSION: The findings of study demonstrate that the therapeutic strategy of vaccination A91-DC is a potential minimally invasive approach that could provide strong neurotrophic factor support after SCI.

Enhancing the performance of Mg-based implant materials by introducing basal plane stacking faults.

One of the keys to allowing Mg alloys to serve as biodegradable materials is how to balance their degradation behaviours and mechanical properties in physiological environment. In this study, a novel Mg-6Ho-0.5Zn alloy (wt%) containing profuse basal plane stacking faults (SFs) is prepared. This newly-developed alloy with SFs exhibiting uniform corrosion behaviour, low corrosion rate and high mechanical properties, as compared to the classic Mg-Ho based alloys (Mg-6Ho and Mg-6Ho-1.5Zn). Furthermore, the Mg-6Ho-0.5Zn alloy shows no significant toxicity to Saos-2 cells. An original uniform corrosion mechanism is proposed by combining the special defect structure, orientation of SFs and promptly effective corrosion film. The development of the new microstructure for Mg-Ho based alloys with desirable corrosion performance has important implications in developing novel degradable Mg-based implant materials.