Strontium Promotes Transforming Growth Factors β1 and β2 Expression in Rat Chondrocytes Cultured In Vitro

Kong, Yezi; Guo, Yazhou; Zhang, Jinfeng; Zhao, Bin; Wang, Jianguo

doi:10.1007/s12011-017-1208-7

Cited by 8 publications

(8 citation statements)

References 33 publications

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“…For instance, Sr-containing α-calcium sulfate hemihydrate promoted osteogenic differentiation through TGFβ1-induced SMAD2/3 phosphorylation ( Liu et al, 2019 ). In addition, in one of our previous studies we demonstrated that Sr can activate TGFβ1 signaling in rat chondrocytes ( Kong et al, 2018 ). Overall, the results of the present study were consistent with the functional link between Sr and TGFβ signaling.…”

Section: Discussionmentioning

confidence: 67%

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Strontium Regulates the Proliferation and Differentiation of Isolated Primary Bovine Chondrocytes via the TGFβ/SMAD Pathway

et al. 2022

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The present study evaluated the effects of strontium (Sr) on proliferation and differentiation of chondrocytes isolated from dairy cows, and whether Sr exerts its effects via transforming growth factor β (TGFβ) signaling. The chondrocytes were isolated from patellar cartilage from newborn Holstein bull calves (n = 3, 1 day old, 38.0 ± 2.8 kg, fasting) within 15 min after euthanasia, and treated with different concentrations of Sr (0, 0.1, 1, and 10 μg/ml, as SrCl2·6H2O). After pretreatment with or without activin receptor-like kinase 5 (ALK5) inhibitor (10 μM SB-505124) for 4 h, chondrocytes were incubated with Sr for another 4 h. Overall effects of Sr were evaluated relative to NaCl as the control. In contrast, the 1 μg/ml Sr-treated group served as the control to determine effects of preincubating with SB-505124. Western blot and qRT-PCR were used for measuring expression of proliferation-, differentiation-, and TGFβ1-responsive factors. Data were analyzed using one-way ANOVA in GraphPad Prism 7.0. Incubation with all doses of Sr increased TGFβ1/ALK5-induced SMAD3 phosphorylation, and at 10 μg/ml it inhibited ALK1-induced SMAD1/5/9 phosphorylation. Expression of mRNA and protein of the proliferation-responsive factors type Ⅱ Collagen α1 (COL2A1) and aggrecan (ACAN) was induced by Sr at 1 μg/ml. In contrast, Sr at 10 μg/ml inhibited the expression of differentiation-responsive factors type Ⅹ Collagen α1 (COL10A1) and secreted phosphoprotein 1 (SPP1), and at 1 μg/ml it had the same effect on alkaline phosphatase (ALPL) mRNA and protein levels. Cells were stained with PI/RNase Staining buffer to assess cell cycle activity using flow-cytometry. Incubation with Sr at 1 and 10 μg/ml induced an increase in the number of cells in the S-phase, leading to an increase in the proliferation index. Incubation with SB-505124 inhibited phosphorylation of SMAD3. Abundance of ACAN and COL2A1 mRNA and protein was lower when cells were pre-incubated with SB-505124. Overall, data indicated that Sr promotes proliferation and inhibits differentiation of primary chondrocytes by directing TGFβ1 signaling towards SMAD3 phosphorylation rather than SMAD1/5/9 phosphorylation. Whether these effects occur in vivo remains to be determined and could impact future application of Sr as an experimental tool in livestock.

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Section: Discussionmentioning

confidence: 67%

“…A previous study reported that Sr can regulate proliferation and differentiation of chondrocytes in rats by promoting the expression of TGFβ1 and TGFβ2 ( Kong et al, 2018 ). However, it is unknown if Sr can mediate the TGFβ pathway to regulate chondrocyte proliferation and differentiation in the bovine.…”

Section: Introductionmentioning

confidence: 99%

Strontium Regulates the Proliferation and Differentiation of Isolated Primary Bovine Chondrocytes via the TGFβ/SMAD Pathway

et al. 2022

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“…Osteoarthritic chondrocytes were isolated from rats in Model, which were euthanasia 4 weeks after surgery, the cells isolation and culture methods were according to a previously described [23,24]. Brie y, after euthanasia, cartilage slices were collected from the proximal tibia and distal femur of OA rats.…”

Section: Isolation and Identi Cation Of Osteoarthritic Chondrocytesmentioning

confidence: 99%

Comparison of the therapeutic effect of BMSCs and culture supernatant injection therapy on osteoarthritis and mechanism exploration

Peng

Zhao

Huang

et al. 2020

Preprint

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Background Osteoarthritis (OA) is a chronic disease that can cause disability. The prevalence of osteoarthritis has increased year by year, become a disease that mainly causes the elderly to suffer. With the increasing understanding of bone marrow mesenchymal stem cell (BMSC) in tissue repair, BMSCs shown good therapeutic effects in OA, it may be due to BMSCs exerted their capacities of differentiation, secretion and immunoregulatory in the joints. As previous describe, BMSCs culture supernatant is proved that rich in multiple cytokines. Therefore, how BMSCs injection therapy exerts its ability to exert therapeutic effects, and whether its therapeutic effect can be replaced by its culture supernatant has become the focus of this article. Methods In vitro, we designed a co-culture system to deepen understand this new stem cell therapy. Through two kinds of cells cultured alone, direct and indirect cell contact co-culture to observe changes in cell morphology, quantity and cytoplasmic glycoprotein of these two types of cells and changes of the level of growth factor in the culture supernatant to explore the interaction of these two types of cells; in vivo, we induced an OA model and Injected Saline solution, BMSCs and their culture supernatants respectively for treatment, then we compared the improvement results of OA by evaluating changes in the cartilage layer after different treatments. And determine the changes of some growth factors and inflammatory factors in synovial fluid to analyze the possible mechanisms of multiple treatments. Result In the co-culture system, it was found that the direct co-culture of BMSCs and OCs can enhance the proliferation ability of OCs, OCs can retain more cytoplasmic glycoprotein, and BMSCs did not occurred abnormal differentiation during the co-culture. In animal experiments, it was found that the ability of BMSCs injection treatment has obvious therapeutic effect on OA, and the effect is better than its supernatant injection treatment. BMSCs therapy reduced matrix loss in articular cartilage cells, and reduced type I collagen production and fibrosis on articular cartilage, effectively regulating EGF and TGF-β1change and inhibited intra-articular inflammation. Supernatant injection treatment will not significantly delay the progress of OA, and it cannot replace BMSCs for the treatment of OA. Conclusion BMSCs therapy is a potential new therapy for OA. The secretion and regulation ability of BMSCs plays an important role in the treatment process. BMSCs are activated by the intra-articular environment of OA, regulating growth factors such as EGF and TGFβ to promote articular cartilage regeneration, and reducing intra-articular inflammation by regulating inflammatory factors and delaying the progression of OA. These effects cannot be replaced by the culture supernatant which is rich in multiple factors, and its regulation function requires the presence of BMSCs. These results provide a relatively comprehensive understanding of BMSCs cell therapy in OA and provide a new explanation for the possible anti-inflammatory effects of BMSCs in the joint.

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“…Sr RAN has been shown to accelerate cartilage regeneration by inhibiting the Wnt/β-catenin signaling pathway [ 17 ] and to stimulate human chondrocytes to synthesize components of the cartilage matrix and alleviate cartilage degradation in osteoarthritis [ 18 ]. In addition, several studies have also established that Sr is involved in regulating chondrocyte maturation [ 19 , 20 , 21 ]. However, research on the effect of Sr in the bones of ruminants is relatively rare.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic and Proteomic Analyses Reveal New Insights into Regulatory Mechanisms of Strontium in Bovine Chondrocytes

Zeng

Yang

et al. 2023

Animals

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Strontium (Sr) is a trace element found mainly in bone, and it performs a dual action by promoting bone formation and inhibiting bone resorption. Sr has been used to evaluate the gastrointestinal calcium (Ca) absorption capacity of dairy cows due to the similar physicochemical properties of the two elements. However, the possible effects of Sr on dairy cows remain unclear. This study aimed to explore the potential regulatory mechanism of Sr in bovine chondrocytes by performing transcriptomic and proteomic analyses. A total of 111 genes (52 up-regulated and 59 down-regulated) were identified as significantly altered (1.2-fold change and p < 0.05) between control and Sr-treated groups. Moreover, LC-MS-based proteomic analysis detected 286 changed proteins (159 up-regulated and 127 down-regulated) between the control and Sr-treated groups (1.2-fold change and p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations of a combination analysis of the transcriptomic and proteomic data revealed that the genes were predominantly involved in chondrocyte proliferation and differentiation, fat metabolism, the inflammation process, and immune responses. Overall, our data reveal a potential regulatory mechanism of strontium in bovine chondrocytes, thus providing further insights into the functions and application of Sr in ruminants.

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Strontium Promotes Transforming Growth Factors β1 and β2 Expression in Rat Chondrocytes Cultured In Vitro

Cited by 8 publications

References 33 publications

Strontium Regulates the Proliferation and Differentiation of Isolated Primary Bovine Chondrocytes via the TGFβ/SMAD Pathway

Strontium Regulates the Proliferation and Differentiation of Isolated Primary Bovine Chondrocytes via the TGFβ/SMAD Pathway

Comparison of the therapeutic effect of BMSCs and culture supernatant injection therapy on osteoarthritis and mechanism exploration

Transcriptomic and Proteomic Analyses Reveal New Insights into Regulatory Mechanisms of Strontium in Bovine Chondrocytes

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