Fas receptor induces apoptosis of synovial bone and cartilage progenitor populations and promotes bone loss in antigen‐induced arthritis

Mosler, Elvira Lazić; Batorek-Lukač, Nina; Flegar, Darja; Fadljević, Martina; Radanović, Igor; Cvija, Hrvoje; Kelava, Tomislav; Ivčević, Sanja; Šućur, Alan; Markotić, Antonio; Katavić, Vedran; Marušić, Ana; Grčević, Danka; Kovačić, Nataša

doi:10.1096/fj.201801426r

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…Therefore, these cell types are vital for the establishment and maintenance of bone remodeling (29). Among them, osteoblasts are a class of bone-forming cells which play a crucial role in bone growth during development and bone formation during remodeling of the postnatal skeleton (13,30). Bone formation depends on the number and activity of osteoblasts in the bone microenvironment (31).…”

Section: Discussionmentioning

confidence: 99%

The regulatory roles of miR-26a in the development of fracture and osteoblasts

Zou¹,

Sun²,

Chen³

et al. 2022

Ann Transl Med

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Background: MicroRNAs (miRNAs) play a vital role in the bone development and bone regeneration. In this study, we investigated the effects of miR-26a in osteoblasts and fractures.Methods: Human osteoblasts were cultured and used for analysis. To identify differential miRNAs in blood samples from patients with fractures and healthy controls, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed. Human osteoblasts were transfected with miR-26a mimics, miR-26a inhibitor, or their corresponding negative controls (NCs), respectively. MTT assay was performed to identify the effects of miR-26a on the cell viability of osteoblasts. EdU staining was applied to detect the proliferation of osteoblasts. Trypan blue staining was utilized to analyze the effects of miR-26a on the cell death of osteoblasts. TUNEL staining was used to detect apoptotic osteoblasts. Alizarin red S (ARS) staining and qRT-PCR analysis were utilized to measure the mineralized nodule formation to evaluate the bone formation of osteoblasts. Dual luciferase reporter assay and western blot analysis were performed to detect the relationship between miR-26a and its target gene. Results:The results of qRT-PCR analysis identified miR-26a as our miRNA of interest and indicated that miR-26a was significantly decreased in patients with fractures. Overexpression of miR-26a significantly increased the cell viability and proliferation of osteoblasts. An increase in miR-26a reduced the cell death and apoptosis of osteoblasts, and promoted the osteoblastic activity and mineralized nodule formation. Dual luciferase reporter assay, qRT-PCR and western blot analysis showed that miR-26a could negatively regulate the expression of phosphatase and tensin homolog (PTEN).Conclusions: MiR-26a promoted new bone regeneration via regulating the functions of osteoblasts by targeting its target gene PTEN. Therefore, we propose that targeting miR-26a may be a novel therapeutic method for bone regeneration and treating fractures.

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Section: Discussionmentioning

confidence: 99%

The regulatory roles of miR-26a in the development of fracture and osteoblasts

Zou¹,

Sun²,

Chen³

et al. 2022

Ann Transl Med

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“…Besides, AIA mice are typically detected with high titers of anti-cyclic citrullinated peptide antibody, and shows severe cartilage injuries. 25 Mice were immunized with 200 mg of mBSA (emulsified in 0.2 mL CFA) by a subcutaneous injection into the flank skin. Seven days after the first injection, the mice were intradermally injected with 100 mg of mBSA in 0.1 mL CFA at the base of the tail.…”

Section: Establishment Of Antigen-induced Arthritis (Aia) Models and ...mentioning

confidence: 99%

“…Arthritis was finally induced on day 21 by an intra-articular injection using 50 mg of mBSA (dissolved in 10 mL sterile phosphate buffer saline) into both knee joint cavities. 25 After the second injection, 28 immunized mice were equally divided into four and received treatments according to grouping: AIA model (0.5% CMC-Na), MG treatment (58 mg/kg), MG (58 mg/ kg) + NAM (72 mg/kg) treatment, and MG (58 mg/kg) + T007097 (15 mg/kg) treatment groups, respectively. Another 7 healthy mice were taken as normal controls.…”

Section: Establishment Of Antigen-induced Arthritis (Aia) Models and ...mentioning

confidence: 99%

α-Mangostin Inhibited M1 Polarization of Macrophages/Monocytes in Antigen-Induced Arthritis Mice by Up-Regulating Silent Information Regulator 1 and Peroxisome Proliferators-Activated Receptor γ Simultaneously

Wu¹,

Zhang²,

Yin³

et al. 2023

DDDT

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Background α-Mangostin (MG) showed the potentials in alleviating experimental arthritis, inhibiting inflammatory polarization of macrophages/monocytes, and regulating peroxisome proliferators-activated receptor γ (PPAR-γ) and silent information regulator 1 (SIRT1) signals. The aim of this study was to analyze the correlations among the above-mentioned properties. Methods Antigen-induced arthritis (AIA) was established in mouse, which was treated with MG in combination with SIRT1/PPAR-γ inhibitors to clarify the role of the two signals in the anti-arthritic actions. Pathological changes were systematically investigated. Phenotypes of cells were investigated by flow cytometry. Expression and co-localization of SIRT1 and PPAR-γ proteins in joint tissues were observed by the immunofluorescence method. Finally, clinical implications from the synchronous up-regulation of SIRT1 and PPAR-γ were validated by experiments in vitro. Results SIRT1 and PPAR-γ inhibitors (nicotinamide and T0070097) reduced the therapeutic effects of MG on AIA mice, and abrogated MG-induced up-regulation of SIRT1/PPAR-γ and inhibition of M1 polarization in macrophages/monocytes. MG has a good binding affinity to PPAR-γ, and MG promoted the co-expression of SIRT1 and PPAR-γ in joints. Synchronously activating SIRT1 and PPAR-γ was revealed to be necessary by MG to repress inflammatory responses in THP-1 monocytes. Conclusion MG binds PPAR-γ and excites this signaling to initiate ligand-dependent anti-inflammatory activity. Due to certain unspecified signal transduction crosstalk mechanism, it then promoted SIRT1 expression and further limited inflammatory polarization of macrophages/monocytes in AIA mice.

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“…Mice were not sensitive to AIA model, and therefore a modified protocol was adopted to ensure the occurrence and severity of AIA in male C57 BL/6 mice by using additional antigen mBSA. [46] Because of that, this model was usually termed as antigen-induced arthritis. CFA) (20 mg mL −1 ) was prepared by finely grinding heat-inactivated BCG in IFA using a porcelain mortar, which was then emulsified with the same volume of mBSA-PBS solution (2 g mL −1 ).…”

Section: Overall Design Of In Vivo Experimentsmentioning

confidence: 99%

Consumption of Saturated Fatty Acids‐Rich Lard Benefits Recovery of Experimental Arthritis by Activating PPAR‐γ

Wang

Feng

et al. 2022

Molecular Nutrition Food Res

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Scope This study investigates the impacts of lard and related fatty acids intake on rheumatoid arthritis (RA) animal models. Method and results Collagen‐induced arthritis (CIA) and adjuvant‐induced arthritis (AIA) are induced in SD rats and C57 BL/6 mice respectively, which are fed by lard‐rich diet (LRD) for 42 days with intake restriction or not. AIA SD rats are treated by representative fatty acids for 30 days. Body weight, arthritis score, and metabolic profile are periodically recorded. Monocyte distribution, cytokine/metabolites levels, gene expression, and tissue damages are investigated by flow cytometry, ELISA, colorimetry, PCR, and histological methods. After being treated by fatty acids in vitro, THP‐1 monocytes and the corresponding medium are collected for ELISA, PCR, immunoblotting, and reporter gene assays. Irrespective of intake amounts, LRD decreases inflammatory cytokines and inhibits glycolysis in all rheumatic rodents. Furthermore, it alters monocyte distribution and promotes PPAR‐γ expression in AIA mice. Overall evidences show that both saturated (SF) and unsaturated fatty acids (USF) from lard can attenuate inflammation by activating PPAR‐γ. Silencing PPAR‐γ abrogates their anti‐inflammatory effects in vitro. Besides, SF can stimulate TLR4/NF‐κB pathway. Conclusion Lard consumption is beneficial for active inflammatory arthritis recovery. Even SF can activate PPAR‐γ and consequently attenuate inflammation.

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Fas receptor induces apoptosis of synovial bone and cartilage progenitor populations and promotes bone loss in antigen‐induced arthritis

Cited by 8 publications

References 51 publications

The regulatory roles of miR-26a in the development of fracture and osteoblasts

The regulatory roles of miR-26a in the development of fracture and osteoblasts

α-Mangostin Inhibited M1 Polarization of Macrophages/Monocytes in Antigen-Induced Arthritis Mice by Up-Regulating Silent Information Regulator 1 and Peroxisome Proliferators-Activated Receptor γ Simultaneously

Consumption of Saturated Fatty Acids‐Rich Lard Benefits Recovery of Experimental Arthritis by Activating PPAR‐γ

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