99Tc‐methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and <scp>CD</scp>4+<scp>CD</scp>25+Foxp3+Tregs

Su, Dinglei; Shen, Minning; Gu, Bin; Wang, Xiaoqin; Wang, Dandan; Li, Xia; Sun, Lingyun

doi:10.1111/1756-185x.12292

Cited by 16 publications

(10 citation statements)

References 24 publications

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“…We also found that the mRNA and protein level of Foxp3 was decreased in the spleens of CIA rats than in normal controls and could be improved by leflunomide both in vivo and in vitro [ 23 ]. These results are consistent with our hypothesis of the involvement of CD4+CD25+Tregs in CIA progression and with the findings of several published studies, which showed an increase of CD4+CD25+Tregs in the therapeutic effect of anti-arthritic drugs on CIA [ 24 , 25 , 26 , 27 ].…”

Section: Discussionsupporting

confidence: 93%

Dynamic Frequency of Blood CD4+CD25+ Regulatory T Cells in Rats with Collagen-induced Arthritis

Jin

et al. 2015

Korean J Physiol Pharmacol

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CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) have been shown to play a regulatory or suppressive role in the immune response and are possibly relevant to the pathogenesis of autoimmune diseases. In the present study, we attempted to investigate the frequency of CD4+CD25+ Tregs in peripheral blood (PB) of collagen-induced arthritis (CIA) rats during the development of arthritis, to determine whether their frequency is involved in the immunoregulation of this disease. The results showed that normal rats had similar frequencies of CD4+CD25+ Tregs in PB during the experiment time, expressed as a percentage of CD4+CD25+Foxp3+ T cells among the CD4+ T lymphocyte population. In contrast, the frequency of CD4+CD25+Foxp3+ T cells in CIA rats was found to change during the development of arthritis. In CIA rats, there is a significant negative correlation between the frequency of CD4+CD25+Foxp3+ T cells and paw swelling (r=-0.786, p< 0.01). The relationship between the frequency of CD4+CD25+Foxp3+ T and immune activation was not found in normal rats. During the time course, the frequency of CD4+CD25+Foxp3+ T was lower in CIA rats than in normal ones. The data suggest that the frequency of PB CD4+CD25+ Tregs may be a promising marker for arthritis activity.

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Section: Discussionsupporting

confidence: 93%

Dynamic Frequency of Blood CD4+CD25+ Regulatory T Cells in Rats with Collagen-induced Arthritis

Jin

et al. 2015

Korean J Physiol Pharmacol

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“…However, among these, there was an increase of Vγ9Vδ2 T cells bearing a terminal effector memory CD27 -CD45RA + phenotype (TEMRA) and a decrease of naïve CD27 + CD45RA + cells [25]. Contrasting with these results, among 19 adults with early active RA, 80% of whom were RF + or anti-cyclic citrullinated peptide (CCP) + and on no current steroid treatment, Vγ9Vδ2 T cells and regulatory T cells (Tregs) were lower, whereas the total percent of γδ T cells was same as in HC [26]. Likewise, among 68 patients with RA (not necessarily designated as early RA), 21 with osteoarthritis (OA) and 21 HC, the percent of γδ T cells in PB was found to be significantly lower in the RA patients, and the percent of Vδ2 + T cells in PB was also decreased in RA relative to OA and HC.…”

Section: Numerical Alterations Of γδ T Cells In Ramentioning

confidence: 91%

“…In this regard, it was further shown that among 19 adults with early active RA, 80% of whom were RF + or CCP + and on no current steroid treatment, treatment with 99Tc-methylene diphosphonate (99Tc-MDP) increased Vγ9δ2 cells and Tregs (which were lower before treatment). Disease activity score (DAS)28, that evaluates disease activity in RA, decreased, as did concentrations of serum TNFα, IL-10, IL-6 during treatment with 99Tc-MDP, whereas IFNγ was unchanged and TGFβ increased [26]. Similarly, among sixty-eight patients with RA, % of Vδ2 T cells in PB correlated inversely with erythrocyte sedimentation rate (ESR), CRP, and DAS28 [27].…”

Section: Relationship To Disease Activity and Severitymentioning

confidence: 98%

The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases

Bank

2020

Cells

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Autoimmune rheumatic diseases (ARDs), affecting ~1–1.5% of all humans, are associated with considerable life long morbidity and early mortality. Early studies in the 1990s showed numerical changes of the recently discovered γδ T cells in the peripheral blood and in affected tissues of patients with a variety of ARDs, kindling interest in their role in the immuno-pathogenesis of these chronic inflammatory conditions. Indeed, later studies applied rapid developments in the understanding of γδ T cell biology, including antigens recognized by γδ T cells, their developmental programs, states of activation, and cytokine production profiles, to analyze their contribution to the pathological immune response in these disorders. Here we review the published studies addressing the role of γδ T in the major autoimmune rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, systemic lupus erythematosus and scleroderma, and animal models thereof. Due to their unique properties spanning adaptive and innate immune functions, the ever deeper understanding of this unique T cell population is shedding new light on the pathogenesis of, while potentially enabling new therapeutic approaches to, these diseases.

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“…It has a stable P‐C‐P bond, which targets to bone tissue, inhibits osteolysis caused by tumor, and promotes the role of bone cell proliferation and differentiation . At present, 99 Tc‐MDP has been widely used to treat autoimmune and osteoarthritic diseases, and can also be used to treat osteoporosis and osteopenia . Clinical studies have shown that 99m Tc‐MDP is well concentrated in the jaw ameloblastomas, and OPG, RANKL, and RANK proteins are expressed in the jaw ameloblastoma .…”

Section: Discussionmentioning

confidence: 99%

Effect of technetium‐99 conjugated with methylene diphosphonate (⁹⁹Tc‐MDP) on OPG/RANKL/RANK system in vitro

Shen

Wang

Yang

et al. 2018

J Oral Pathology Medicine

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Background RANKL and RANK play an important role in jaw resorption during the development of the ameloblastomas. Therefore, the aim of this study was to explore the effect of 99Tc‑MDP on OPG/RANKL/RANK system on RAW264.7 and MC3T3‐E1 cell lines in vitro and provide the theoretical basis for the clinical treatment of the jaw ameloblastoma. Methods Different concentrations of 99Tc‐MDP were used to treat RAW264.7 and MC3T3‐E1 cell lines. The cell proliferative inhibition rate was analyzed by CCK‐8. Cell apoptosis and cell cycle were detected by flow cytometry. Western blot was used to detect the expression of OPG, RANKL, and RANK. Results Treatment of RAW264.7 cell lines with different concentrations of 99Tc‐MDP had inhibitory effects and decreased the expression of RANK protein. The cell proliferation of 99Tc‐MDP on MC3T3‐E1 cell lines was stronger at 48 hours than at 24 hours except for 100 μg/mL concentration group. Compared with the concentration of 0.01 μg/mL, the treatment of MC3T3‐E1 cells with 100 μg/mL 99Tc‐MDP showed that the cell proliferative effect decreased at 24 hours and 48 hours (P < 0.05). After treatment with 0.01 μg/mL 99Tc‐MDP, the expression of OPG in MC3T3‐E1 cells was significantly increased (P < 0.05). Compared with 0.01 μg/mL, the expression of RANKL was decreased after treatment with 100 μg/mL 99Tc‐MDP (P < 0.05). Conclusion 99Tc‐MDP can induce apoptosis of RAW264.7 cells and inhibit the expression of RANK protein. The effect of 0.01 μg/mL of low concentration of 99Tc‐MDP can promote the proliferation of MC3T3‐E1 cells and increase the expression of OPG and RANKL protein. 99Tc‐MDP may have adjuvant therapeutic effects on the treatment of jaw ameloblastoma.

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⁹⁹Tc‐methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and CD4⁺CD25⁺Foxp3⁺Tregs

Abstract: Aim: cd T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the cd T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As

Cited by 16 publications

References 24 publications

Dynamic Frequency of Blood CD4+CD25+ Regulatory T Cells in Rats with Collagen-induced Arthritis

Dynamic Frequency of Blood CD4+CD25+ Regulatory T Cells in Rats with Collagen-induced Arthritis

The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases

Effect of technetium‐99 conjugated with methylene diphosphonate (⁹⁹Tc‐MDP) on OPG/RANKL/RANK system in vitro

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99Tc‐methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and CD4+CD25+Foxp3+Tregs

Abstract: Aim: cd T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the cd T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As

Cited by 16 publications

References 24 publications

Dynamic Frequency of Blood CD4+CD25+ Regulatory T Cells in Rats with Collagen-induced Arthritis

Dynamic Frequency of Blood CD4+CD25+ Regulatory T Cells in Rats with Collagen-induced Arthritis

The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases

Effect of technetium‐99 conjugated with methylene diphosphonate (99Tc‐MDP) on OPG/RANKL/RANK system in vitro

Contact Info

Product

Resources

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⁹⁹Tc‐methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and CD4⁺CD25⁺Foxp3⁺Tregs

Effect of technetium‐99 conjugated with methylene diphosphonate (⁹⁹Tc‐MDP) on OPG/RANKL/RANK system in vitro