Potential diagnostic value of PD‐1 in peripheral blood mononuclear cells of postmenopausal osteoporosis patients

Cai, Xiuping; Zhao, Qing; Guo, Zhaodi; Lin, Shao‐Jun; Chen, Zhixiang; Chen, Minyuan; Zhao, Ke

doi:10.1002/jcla.23223

Cited by 4 publications

(10 citation statements)

References 21 publications

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“…Concentrating on the remaining molecules (Figure 2B), the greatest increase in the cell size of TRAP + cells to 4516 µm 2 was registered for TIGIT antibody, followed by GITR protein (4106 µm 2 ) and Tim-3 antibody stimulation (3894 µm 2 ). In contrast, a significant decrease in average cell size was seen for the TIGIT protein (1369 µm 2 ) and the Tim-3 protein (1057 µm 2 ). Treatment with the GITR and CD47 antibodies as well as the CD47 protein did not lead to any significant changes in cell size (2947 µm 2 , 2357 µm 2 and 3278 µm 2 , respectively).…”

Section: Average Size Of Trap + Cellsmentioning

confidence: 88%

“…It is widely accepted to compare bone resorption by OCs (as professional phagocytes) to macrophage phagocytosis during pro-inflammatory M1 polarization ( 37 – 40 ). Such consideration is even more reasonable owing to PD-1 being significantly upregulated in PBMCs of patients suffering from postmenopausal osteoporosis, which represents an imbalance in the OC/OB activity ratio and further correlates with elevated C-reactive protein (CRP) levels ( 2 ). Hence, PD-1 is thought to favor OC maturation not only via the inhibition of osteoblastic bone formation but also by upregulating OC activity as well as inflammatory mediators ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…The average size of a TRAP + cell in the control group was 2669 µm 2 . All comparisons for the group of PD-1 related checkpoints (Figure 2A) were significant.…”

Section: Average Size Of Trap + Cellsmentioning

confidence: 98%

“…The current diagnostic and therapeutical management for diseases such as osteoporosis, aseptic loosening of endoprostheses, and certain cancers is insufficient. However, there is evidence about underlying osteoimmunological mechanisms that are immensely relevant in development of osteoporotic conditions and skeletal fractures (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

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Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis

Brom

Strauß²,

Sieberath³

et al. 2023

Front. Immunol.

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IntroductionImmune checkpoint inhibitors are used in the treatment of various cancers and have been extensively researched with regard to inflammatory and autoimmune diseases. However, this revolutionary therapeutic strategy often provokes critical auto-inflammatory adverse events, such as inflammatory reactions affecting the cardiovascular, gastrointestinal, nervous, and skeletal systems. Because the function of these immunomodulatory co-receptors is highly cell-type specific and the role of macrophages as osteoclast precursors is widely published, we aimed to analyze the effect of immune checkpoint inhibitors on these bone-resorbing cells.MethodsWe established an in vitro model of osteoclastogenesis using human peripheral blood mononuclear cells, to which various immune checkpoints and corresponding antagonistic antibodies were administered. Formation of osteoclasts was quantified and cell morphology was analyzed via immunofluorescence staining, cell size measurements, and calculation of cell numbers in a multitude of samples.ResultsThese methodical approaches for osteoclast research achieved objective, comparable, and reproducible results despite the great heterogeneity in the form, size, and number of osteoclasts. In addition to the standardization of experimental analyses involving osteoclasts, our study has revealed the substantial effects of agonistic and antagonistic checkpoint modulation on osteoclastogenesis, confirming the importance of immune checkpoints in bone homeostasis.DiscussionOur work will enable more robust and reproducible investigations into the use of immune checkpoint inhibitors in conditions with diminished bone density such as osteoporosis, aseptic loosening of endoprostheses, cancer, as well as the side effects of cancer therapy, and might even pave the way for novel individualized diagnostic and therapeutic strategies.

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Section: Average Size Of Trap + Cellsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

“…The average size of a TRAP + cell in the control group was 2669 µm 2 . All comparisons for the group of PD-1 related checkpoints (Figure 2A) were significant.…”

Section: Average Size Of Trap + Cellsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis

Brom

Strauß²,

Sieberath³

et al. 2023

Front. Immunol.

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“… 2 Previous studies report that higher programmed cell death protein 1 (PD‐1) and systemic immune‐inflammation index (SII) in the peripheral blood of PMOP patients have potential diagnostic application for PMOP. 3 , 4 Although sensitive and effective biomarkers have been identified for early identification of PMOP, current treatment strategies do not fully reverse osteoporosis. Bone marrow‐derived mesenchymal stem cells (BMSCs) promoted bone regeneration and play important roles in maintaining normal bone metabolism.…”

Section: Introductionmentioning

confidence: 99%

Microarray analysis of circRNAs sequencing profile in exosomes derived from bone marrow mesenchymal stem cells in postmenopausal osteoporosis patients

Fang

Xiang

et al. 2021

Clinical Laboratory Analysis

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Introduction: Bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomes are involved in the modulation of tissue repair and regeneration. CircRNAs play important roles in BMSCs exosomes. The current study sought to explore the role of circRNAs in exosomes derived from BMSCs of postmenopausal osteoporosis (PMOP) patients and the underlying mechanisms.Methods: RNA was extracted from BMSCs exosomes of PMOP and a control group.RNA microarray and bioinformatics analyses were used to explore the expression profile and functions circRNAs. Differentially expressed circRNAs from 20 PMOP and 20 controls were analyzed using RT-qPCR.Results: A total of 237 upregulated and 279 downregulated circRNAs were identified in the current study. The top-10 most upregulated circRNAs in the PMOP group were hsa_circ_0069691, hsa_circ_0005678, hsa_circ_0006464, hsa_circ_0015813, hsa_circ_0000511, hsa_circ_0076527, hsa_circ_0009127, hsa_circ_0047285, hsa_ circ_0027741, and hsa_circ_0090949. The top-10 most downregulated circRNAs were hsa_circ_0048669, hsa_circ_0090247, hsa_circ_0070899, hsa_circ_0087557, hsa_circ_0045963, hsa_circ_0090180, hsa_circ_0058392, hsa_circ_0040751, hsa_ circ_0067910, and hsa_circ_0049484. RT-PCR verified dysregulation of 5 circRNAs including hsa_circ_0009127, hsa_circ_0090759, hsa_circ_0058392, hsa_circ_0090247, and hsa_circ_0049484. Moreover, a circRNA-microRNA-mRNA interaction network was developed based on differentially expressed circRNAs. Functional analysis showed that pathways involved in the regulation of autophagy, PI3K-Akt signaling, FoxO signaling, and MAPK signaling were associated with the differentially expressed circRNAs in PMOP patients. Conclusion:The findings of this study show dysregulated circRNAs in BMSCs exosomes of PMOP patients, which may affect the progression of PMOP. These circR-NAs can be used as predictive biomarkers and as therapeutic targets for the treatment of PMOP.

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Immune checkpoint inhibitors: friend or foe for osteoporosis

Tang

2023

Therapeutic Advances in Endocrinology

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Potential diagnostic value of PD‐1 in peripheral blood mononuclear cells of postmenopausal osteoporosis patients

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 4 publications

References 21 publications

Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis

Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis

Microarray analysis of circRNAs sequencing profile in exosomes derived from bone marrow mesenchymal stem cells in postmenopausal osteoporosis patients

Immune checkpoint inhibitors: friend or foe for osteoporosis

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