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The Link between Osteoporosis and Frozen Shoulder: Exploring the Therapeutic Effect of TAK715 on Reversing Fibrosis and Protecting against Osteoporosis via the p38 MAPK Signaling Pathway

ABSTRACT: The Link between Osteoporosis and Frozen Shoulder: Exploring the Therapeutic Effect of TAK715 on Reversing Fibrosis and Protecting against Osteoporosis via the p38 MAPK Signaling Pathway

PROVIDER: PRJNA1104624 | ENA |

REPOSITORIES: ENA

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The Link between Osteoporosis and Frozen Shoulder: Exploring the Therapeutic Effect of TAK715 on Reversing Fibrosis and Protecting against Osteoporosis via the p38 MAPK Signaling Pathway

Project description:The global incidence of frozen shoulder (FS) and osteoporosis (OP) is high. Although FS patients may experience localized OP in the shoulder, there is still insufficient strong evidence to confirm the relationship between FS and OP. The main objective of this current research is to investigate the pathogenesis mechanism of FS and explore the connection between FS and OP.We obtained FS and OP datasets from GEO and identified crosstalk genes. We screened the p38 MAPK signaling pathway and its specific inhibitor, TAK715. We conducted flow cytometry, western blot, and PCR analyses to assess the treatment effect of TAK715 on FS synovium fibroblasts at concentrations of 1μM, 5μM, and 10μM. Additionally, we employed SD rats to validate the treatment effects of TAK715 in vivo. TAK715 was found to also intervene in the activation of osteoclasts. We successfully established a FS and OP rat model, with the FS with OP rat displaying more severe symptoms. Results demonstrated that TAK715 effectively corrected both fibrosis and osteoporosis simultaneously in vivo.The frozen shoulder with osteoporosis may exhibit more severe symptoms, and TAK715 is effective in protecting fibrosis and osteoporosis both in vitro and vivo. The therapy to correct FS and OP simultaneously by TAK715 provides novel approach in FS treatment and study.

2024-04-27 | GSE265890 | GEO

MicrRNA-26a deficiency attenuates the severity of frozen shoulder in a mouse immobilization model

Project description:The main pathogenesis of the frozen shoulder is thought to be the inflammation of the intra-articular synovium and subsequent fibrosis of the shoulder joint capsule. However, the molecular pathogenesis of the frozen shoulder is still unknown. A class of non-coding RNAs, microRNAs (miRNAs) contribute to various diseases including musculoskeletal diseases. MicroRNA-26a (miR-26a) has been reported to be associated with fibrosis in several organs. This study aims to reveal the role of miR-26a on fibrosis in the shoulder capsule using a frozen shoulder model in miR-26a deficient (miR-26a KO) mice. MiR-26 KO and wild type (WT) mice were investigated using a frozen shoulder model. The range of motion of the shoulder, histopathological analysis such as synovitis, and fibrosis related-genes expression in the model mice were evaluated to determine the role of miR-26a. In WT mice, both inflammatory cell infiltration and thickening of the inferior shoulder joint capsule were observed after 1 week of immobilization, and this thickening further progressed over the subsequent 6 weeks. However, the immobilized shoulder in miR-26a KO mice consistently exhibited significantly better range of motion compared with WT mice at each point, and histological changes were notably less severe. The expression of inflammation- and fibrosis-related genes was decreased in the miR-26a KO mice compared with WT mice at 1 and 6 weeks. Together, miR-26a deficiency attenuated the severity of frozen shoulder in the immobilization model mouse. The present study suggests that miR-26a has the potential to be a target miRNA for therapeutic approach to frozen shoulder.

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A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Project description:Single cell transcriptomic data of shoulder capsule from foetal, adult comparator (normal) and frozen shoulder (disease).

2023-10-02 | E-MTAB-12304 | biostudies-arrayexpress

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution (Bulk RNA-seq of capsular fibroblasts co-cultured with MDMs)

Project description:Bulk transcriptomic data of shoulder capsule fibroblasts isolated from frozen shoulder co-cultured with Dexamethasone (DEX) or LPS treated monocyte-derived macrophages (MDM), which were isolated from blood cones and stimulated with M-CSF, for 72 hours. The stimulated MDMs have been characterised as MerTKhigh(DEX) and MerTKlow(LPS). Unstimulated, DEX and LPS stimulated MDM were co-cultured with ex vivo shoulder capsule-derived fibroblasts from patients with frozen shoulder. Fibroblasts were then FACS isolated and RNA-sequencing analysis performed. As an additional control ex vivo fibroblasts were also profiled without co-culture (stimulation=”none”).

2023-10-02 | E-MTAB-12312 | biostudies-arrayexpress

Tuina reverses capsule fibrosis in Frozen Shoulder as indicated via phosphoproteomics

Project description:Frozen shoulder (FS) is a common disorder often treated with Tuina, but the mechanisms involved remain unclear. We employed proteomics to investigate the mechanisms associated with the treatment of capsule fibrosis in FS rats. We used a method composed of three weeks of cast immobilization to establish a model of FS. We then administered Tuina once daily for 14 days, identified differentially expressed proteins (DEPs) using phosphoproteomics. Then we used bioinformatics methods to study the mechanism of tuina therapy

2024-01-09 | PXD047468 | Pride

Tuina reverses capsule fibrosis in Frozen Shoulder as indicated via protemocis

Project description:Frozen shoulder (FS) is a common disorder often treated with Tuina, but the mechanisms involved remain unclear. We employed proteomics to investigate the mechanisms associated with the treatment of capsule fibrosis in FS rats. We used a method composed of three weeks of cast immobilization to establish a model of FS. We then administered Tuina once daily for 14 days, identified differentially expressed proteins (DEPs) using proteomics. Then we used bioinformatics methods to study the mechanism of tuina therapy

2024-01-09 | PXD047467 | Pride

Homo sapiens

Project description:The Link between Osteoporosis and Frozen Shoulder: Exploring the Therapeutic Effect of TAK715 on Reversing Fibrosis and Protecting against Osteoporosis via the p38 MAPK Signaling Pathway

| PRJNA1100765 | ENA

Frozen shoulder.

Project description: Not available

| S-EPMC1315655 | biostudies-literature

Transcriptomic analysis of adhesive capsulitis of the shoulder

Project description:We compared genes from tissue of patients with adhesive capsulitis (AC) with those having surgery for shoulder instability to determine potential biomarkers specific to AC through transcriptomic analysis. Our results presented increased expression of PDGFB, COL18A1 and MMP9 in patients with AC, while TNFA expression was reduced.

2019-11-21 | GSE140731 | GEO

Detection of potential microRNA biomarker for postmenopausal osteoporosis

Project description:Recent studies have shown that microRNAs (miRNAs) are implicated in the development of postmenopausal osteoporosis, implying potential biomarkers. We performed a microarray-based expression scanning to search for potential circulating miRNA biomarkers for postmenopausal osteoporosis as whole blood obtianed from patients was used. MiRNA expression in the whole blood of 23 Chinese postmenopausal women with osteopenia and that of 25 Chinese postmenopausal women with osteoporosis. After total RNA was extracted, all of the RNA extraction samples were seperately pooled into six subgroups according to the T-score measurement.

2014-12-23 | E-GEOD-64433 | biostudies-arrayexpress

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