<i>LRRC17</i> regulates the bone metabolism of human bone marrow mesenchymal stem cells from patients with idiopathic necrosis of femoral head through Wnt signaling pathways: A preliminary report

Song, Da; Wu, Zhensong; Xu, Qi; Wang, Kai; Xu, Mingtao; Ha, Chengzhi; Zhang, Chao; Wang, Dawei

doi:10.3892/etm.2021.10098

Cited by 6 publications

(7 citation statements)

References 32 publications

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“…LRRC17 was reported to regulate bone metabolism through the Wnt signalling pathway to prevent osteoporosis. 41 EFEMP2 is the downstream negative regulatory target of miR-211-5p, which was involved in chondrocyte differentiation and can reduce the expression level of proinflammatory cytokines. 42 At present, there is no literature report on the relationship between SPEN and OA and DM.…”

Section: Discussionmentioning

confidence: 99%

Identification of the shared genes in type 2 diabetes mellitus and osteoarthritis and the role of quercetin

Song,

2024

J Cellular Molecular Medi

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This study investigated the underlying comorbidity mechanism between type 2 diabetes mellitus (T2DM) and osteoarthritis (OA), while also assessing the therapeutic potential of quercetin for early intervention and treatment of these two diseases. The shared genes were obtained through GEO2R, limma and weighted gene co‐expression network analysis (WGCNA), and validated using clinical databases and the area under the curves (ROC). Functional enrichment analysis was conducted to elucidate the underlying mechanisms of comorbidity between T2DM and OA. The infiltration of immune cells was analysed using the CIBERSORT algorithm in conjunction with ESTIMATE algorithm. Subsequently, transcriptional regulation analysis, potential chemical prediction, gene‐disease association, relationships between the shared genes and ferroptosis as well as immunity‐related genes were investigated along with molecular docking. We identified the 12 shared genes (EPHA3, RASIP1, PENK, LRRC17, CEBPB, EFEMP2, UBAP1, PPP1R15A, SPEN, MAFF, GADD45B and KLF4) across the four datasets. Our predictions suggested that targeting these shared genes could potentially serve as therapeutic interventions for both T2DM and OA. Specifically, they are involved in key signalling pathways such as p53, IL‐17, NF‐kB and MAPK signalling pathways. Furthermore, the regulation of ferroptosis and immunity appears to be interconnected in both diseases. Notably, in this context quercetin emerges as a promising drug candidate for treating T2DM and OA by specifically targeting the shared genes. We conducted a bioinformatics analysis to identify potential therapeutic targets, mechanisms and drugs for T2DM and OA, thereby offering novel insights into molecular therapy for these two diseases.

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Section: Discussionmentioning

confidence: 99%

Identification of the shared genes in type 2 diabetes mellitus and osteoarthritis and the role of quercetin

Song,

2024

J Cellular Molecular Medi

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“…LRRC17 prevents the activation of RANK-L-dependent osteoclasts, thus protecting against osteoporotic phenotypes. In fact, the risk of postmenopausal women experiencing osteoporotic fractures was found to be 46% higher in those with lower LRRC17 levels than those with higher levels [ 25 ]. The downregulation of the LRRC17 protein in OA synovial fluid may reflect an affected pathway that is shared by the pathology of osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Female Synovial Fluid to Identify Novel Biomarkers for Osteoarthritis

Müller

Lee

Zhi

et al. 2023

Life

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Osteoarthritis (OA) is a highly prevalent degenerative joint condition that disproportionately affects females. The pathophysiology of the disease is not well understood, which makes diagnosis and treatment difficult. Given the physical connection of synovial fluid (SF) with articular tissues, the SF’s composition can reflect relevant biological modifications, and has therefore been a focus of research. Previously, we demonstrated that extracellular vesicles isolated from the synovial fluid of OA patients carry different cargo (protein and miRNA) in a sex-specific manner. Given the increased prevalence and severity of OA in females, this study aims to identify differential protein content within the synovial fluid of female OA and non-osteoarthritic (non-OA) patients. We found that several proteins were differentially expressed in osteoarthritic females compared with age-matched controls. Presenilin, Coagulation Factor X, Lysine-Specific Demethylase 2B, Tenascin C, Leucine-Rich Repeat-Containing Protein 17 fragments, and T-Complex Protein 1 were negatively regulated in the OA group, with PGD Synthase, Tubulointerstitial Nephritis Antigen, and Nuclear Receptor Binding SET Domain Protein 1 positively regulated in the OA group. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analyses established these proteins as significantly involved in many biological, cellular, and molecular processes. In conclusion, the protein content of female synovial fluid is altered in OA patients, which is likely to provide insights into gender-specific pathophysiology.

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“…A number of studies have indicated that LRRC17 overexpression induces reduced osteogenic ability and bone mass. [43][44][45][46] Liu et al [47] further revealed that LRRC17 overexpression in BMSCs impairs autophagy, which decreases the osteogenic ability of BMSCs. It is worth investigating the underlying mechanisms through which these genes influence the osteogenic ability and bone mass of AIS-related osteopenia patients.…”

Section: Discussionmentioning

confidence: 99%

“…Roy et al [42] suggested that the expression of DCLK1, which is involved in the survival and progression of colon tumors, impairs the process of autophagy. A number of studies have indicated that LRRC17 overexpression induces reduced osteogenic ability and bone mass [43–46] . Liu et al [47] further revealed that LRRC17 overexpression in BMSCs impairs autophagy, which decreases the osteogenic ability of BMSCs.…”

Section: Discussionmentioning

confidence: 99%

Impaired autophagy activity-induced abnormal differentiation of bone marrow stem cells is related to adolescent idiopathic scoliosis osteopenia

Zhang

Yang

et al. 2022

Chinese Medical Journal

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Background: Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS). Bone marrow stem cells (BMSCs) are a crucial regulator of bone homeostasis. Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia, but the underlying mechanism of this phenomenon remains unclear. Methods: A total of 22 AIS patients and 18 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Bone marrow blood was collected for BMSC isolation and culture. Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group. Furthermore, a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis.Results: A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed. Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified, including differences in the expression of LRRC17, DCLK1, PCDH7, TSPAN5, NHSL2, and CPT1B. Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy. The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group. Conclusion: Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity, which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.

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LRRC17 regulates the bone metabolism of human bone marrow mesenchymal stem cells from patients with idiopathic necrosis of femoral head through Wnt signaling pathways: A preliminary report

Cited by 6 publications

References 32 publications

Identification of the shared genes in type 2 diabetes mellitus and osteoarthritis and the role of quercetin

Identification of the shared genes in type 2 diabetes mellitus and osteoarthritis and the role of quercetin

Proteomic Analysis of Female Synovial Fluid to Identify Novel Biomarkers for Osteoarthritis

Impaired autophagy activity-induced abnormal differentiation of bone marrow stem cells is related to adolescent idiopathic scoliosis osteopenia

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