Altered Secretome of Diabetic Monocytes Could Negatively Influence Fracture Healing—An In Vitro Study

Savini, Lorena; Rollmann, Mika F.; Histing, Tina; Nüssler, Andreas K.; Ehnert, Sabrina

doi:10.3390/ijms22179212

Cited by 6 publications

(10 citation statements)

References 68 publications

(91 reference statements)

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“…The PBMC (upper) layer was transferred to a new tube. After washing twice with PBS, the cells were counted and seeded at a concentration of 5 × 10 5 cells/mL in an RPMI 1640 medium with 2% autologous plasma [ 28 ]. Experiments were performed at 37 °C (5% CO 2 , humidified atmosphere).…”

Section: Methodsmentioning

confidence: 99%

“…Chemiluminescent signals were detected with the ChemoCam and quantified using ImageJ software. The data were normalized to the internal controls [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Immediately, an image was taken with the microscope to document the time point 0 h. After 48 h, SRB staining was performed for better visualization of SCP-1 cells. The “gap closure” in the microscopic images was calculated and analyzed using ImageJ software [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Adherent cells were fixed with ice-cold 99% EtOH for at least 1 h at −20 • C. After washing the plates with tap water, the cells were covered with SRB solution (0.4% SRB in 1% acetic acid) for 30 min. The unbound SRB was removed by washing with 1% acetic acid [28].…”

Section: Sulforhodamine B (Srb) Stainingmentioning

confidence: 99%

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Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing

et al. 2021

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Delayed fracture healing and fracture non-unions impose an enormous burden on individuals and society. Successful healing requires tight communication between immune cells and bone cells. Macrophages can be found in all healing phases. Due to their high plasticity and long life span, they represent good target cells for modulation. In the past, extremely low frequency pulsed electromagnet fields (ELF-PEMFs) have been shown to exert cell-specific effects depending on the field conditions. Thus, the aim was to identify the specific ELF-PEMFs able to modulate macrophage activity to indirectly promote mesenchymal stem/stromal cell (SCP-1 cells) function. After a blinded screening of 22 different ELF-PEMF, two fields (termed A and B) were further characterized as they diversely affected macrophage function. These two fields have similar fundamental frequencies (51.8 Hz and 52.3 Hz) but are emitted in different groups of pulses or rather send–pause intervals. Macrophages exposed to field A showed a pro-inflammatory function, represented by increased levels of phospho-Stat1 and CD86, the accumulation of ROS, and increased secretion of pro-inflammatory cytokines. In contrast, macrophages exposed to field B showed anti-inflammatory and pro-healing functions, represented by increased levels of Arginase I, increased secretion of anti-inflammatory cytokines, and growth factors are known to induce healing processes. The conditioned medium from macrophages exposed to both ELF-PEMFs favored the migration of SCP-1 cells, but the effect was stronger for field B. Furthermore, the conditioned medium from macrophages exposed to field B, but not to field A, stimulated the expression of extracellular matrix genes in SCP-1 cells, i.e., COL1A1, FN1, and BGN. In summary, our data show that specific ELF-PEMFs may affect immune cell function. Thus, knowing the specific ELF-PEMFs conditions and the underlying mechanisms bears great potential as an adjuvant treatment to modulate immune responses during pathologies, e.g., fracture healing.

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Section: Methodsmentioning

confidence: 99%

“…Chemiluminescent signals were detected with the ChemoCam and quantified using ImageJ software. The data were normalized to the internal controls [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Sulforhodamine B (Srb) Stainingmentioning

confidence: 99%

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Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing

et al. 2021

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“…Staining was resolved with 10 mM of unbuffered Tris solution and absorbance was measured at 565 nm and 690 nm with the Omega plate reader. The absorbance values at 690 nm (impurities) were subtracted from the values at 565 nm [50].…”

Section: Srb Stainingmentioning

confidence: 99%

Febrile-Range Hyperthermia Can Prevent Toxic Effects of Neutrophil Extracellular Traps on Mesenchymal Stem Cells

Nüssler

Histing

Ehnert

2022

IJMS

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Fracture healing is characterized by an inflammatory phase directly after fracture which has a strong impact on the healing outcome. Neutrophils are strong contributors here and can release neutrophil extracellular traps (NETs). NETs are found after trauma, originally thought to capture pathogens. However, they can lead to tissue damage and impede wound healing processes. Their role in fracture healing remains unclear. In this study, the effect of isolated NETs on the function of bone-forming mesenchymal stem cells (SCP-1 cells) was examined. NETs were isolated from stimulated healthy neutrophils and viability, migration, and differentiation of SCP-1 cells were analyzed after the addition of NETs. NETs severely impaired the viability of SCP-1 cells, induced necrosis and already nontoxic concentrations reduced migration significantly. Short-term incubation with NETs had a persistent negative effect on osteogenic differentiation, as measured by AP activity and matrix formation. The addition of DNase or protease inhibitors failed to reverse the negative effect of NETs, whereas a short febrile-range temperature treatment successfully reduced the toxicity and membrane destruction. Thus, the possible modification of the negative effects of NETs in fracture hematomas could be an interesting new target to improve bone healing, particularly in patients with chronic diseases such as diabetes.

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Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study

Zheng,

Lin,

Wang

et al. 2024

JOR Spine

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BackgroundNumerous investigations have suggested links between circulating inflammatory proteins (CIPs) and spinal degenerative diseases (SDDs), but causality has not been proven. This study used Mendelian randomization (MR) to investigate the causal associations between 91 CIPs and cervical spondylosis (CS), prolapsed disc/slipped disc (PD/SD), spinal canal stenosis (SCS), and spondylolisthesis/spondylolysis.MethodsGenetic variants data for CIPs and SDDs were obtained from the genome‐wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary method, analyzing the validity and robustness of the results through pleiotropy and heterogeneity tests and performing reverse MR analysis to test for reverse causality.ResultsThe IVW results with Bonferroni correction indicated that beta‐nerve growth factor (β‐NGF), C‐X‐C motif chemokine 6 (CXCL6), and interleukin‐6 (IL‐6) can increase the risk of CS. Fibroblast growth factor 19 (FGF19), sulfotransferase 1A1 (SULT1A1), and tumor necrosis factor‐beta (TNF‐β) can increase PD/SD risk, whereas urokinase‐type plasminogen activator (u‐PA) can decrease the risk of PD/SD. FGF19 and TNF can increase SCS risk. STAM binding protein (STAMBP) and T‐cell surface glycoprotein CD6 isoform (CD6 isoform) can increase the risk of spondylolisthesis/spondylolysis, whereas monocyte chemoattractant protein 2 (MCP2) and latency‐associated peptide transforming growth factor beta 1 (LAP‐TGF‐β1) can decrease spondylolisthesis/spondylolysis risk.ConclusionsMR analysis indicated the causal associations between multiple genetically predicted CIPs and the risk of four SDDs (CS, PD/SD, SCS, and spondylolisthesis/spondylolysis). This study provides reliable genetic evidence for in‐depth exploration of the involvement of CIPs in the pathogenic mechanism of SDDs and provides novel potential targets for SDDs.

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Altered Secretome of Diabetic Monocytes Could Negatively Influence Fracture Healing—An In Vitro Study

Cited by 6 publications

References 68 publications

Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing

Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing

Febrile-Range Hyperthermia Can Prevent Toxic Effects of Neutrophil Extracellular Traps on Mesenchymal Stem Cells

Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study

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