scholarly journals Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

2020 ◽  
Vol 21 (8) ◽  
pp. 2904
Author(s):  
Yuhan Chang ◽  
Yi-min Hsiao ◽  
Chih-Chien Hu ◽  
Chih-Hsiang Chang ◽  
Cai-Yan Li ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Bone Loss ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Osteoclast Differentiation ◽  
Mapk Signaling ◽  
Calcium Deposition ◽  
Tartrate Resistant Acid Phosphatase ◽  
Activation Markers ◽  
Osteoclast Activation

Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.

scholarly journals Kalkitoxin Reduces Osteoclast Formation and Resorption and Protects against Inflammatory Bone Loss

2021 ◽  
Vol 22 (5) ◽  
pp. 2303
Author(s):  
Liang Li ◽  
Ming Yang ◽  
Saroj Kumar Shrestha ◽  
Hyoungsu Kim ◽  
William H. Gerwick ◽  
...  
Keyword(s):  
Bone Loss ◽  
Transmembrane Protein ◽  
Osteoclast Differentiation ◽  
Mapk Signaling ◽  
Osteoclast Formation ◽  
Bone Diseases ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Mineral Density ◽  
Multinucleated Cells

Osteoclasts, bone-specified multinucleated cells produced by monocyte/macrophage, are involved in numerous bone destructive diseases such as arthritis, osteoporosis, and inflammation-induced bone loss. The osteoclast differentiation mechanism suggests a possible strategy to treat bone diseases. In this regard, we recently examined the in vivo impact of kalkitoxin (KT), a marine product obtained from the marine cyanobacterium Moorena producens (previously Lyngbya majuscula), on the macrophage colony-stimulating factor (M-CSF) and on the receptor activator of nuclear factor κB ligand (RANKL)-stimulated in vitro osteoclastogenesis and inflammation-mediated bone loss. We have now examined the molecular mechanism of KT in greater detail. KT decreased RANKL-induced bone marrow-derived macrophages (BMMs) tartrate-resistant acid phosphatase (TRAP)-multinucleated cells at a late stage. Likewise, KT suppressed RANKL-induced pit area and actin ring formation in BMM cells. Additionally, KT inhibited several RANKL-induced genes such as cathepsin K, matrix metalloproteinase (MMP-9), TRAP, and dendritic cell-specific transmembrane protein (DC-STAMP). In line with these results, RANKL stimulated both genes and protein expression of c-Fos and nuclear factor of activated T cells (NFATc1), and this was also suppressed by KT. Moreover, KT markedly decreased RANKL-induced p-ERK1/2 and p-JNK pathways at different time points. As a result, KT prevented inflammatory bone loss in mice, such as bone mineral density (BMD) and osteoclast differentiation markers. These experiments demonstrated that KT markedly inhibited osteoclast formation and inflammatory bone loss through NFATc1 and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, KT may have potential as a treatment for destructive bone diseases.

scholarly journals Synovial Complement Factors in Patients with Periprosthetic Joint Infection after Undergoing Revision Arthroplasty of the Hip or Knee Joint

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 434
Author(s):  
Frank Sebastian Fröschen ◽  
Sophia Schell ◽  
Matthias Dominik Wimmer ◽  
Gunnar Thorben Rembert Hischebeth ◽  
Hendrik Kohlhof ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Multiple Regression ◽  
Complement System ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Expression Patterns ◽  
Factor H ◽  
Low Grade ◽  
Complement Factors ◽  
Fluid Levels

The role and diagnostic value of the synovial complement system in patients with low-grade periprosthetic joint infection (PJI) are unclear. We sought to evaluate, for the first time, the usefulness of synovial complement factors in these patients by measuring the individual synovial fluid levels of complement factors (C1q, C3b/iC3b, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, properdin, and mannose-binding lectin [MBL]). The patients (n = 74) were classified into septic (n = 28) and aseptic (n = 46). Receiver-operator characteristic curves and a multiple regression model to determine the feasibility of a combination of the tested cytokines to determine the infection status were calculated. The synovial fluid levels of C1q, C3b/C3i, C4b, C5, C5a, MBL, and properdin were significantly elevated in the PJI group. The best sensitivity and specificity was found for C1q. The multiple regression models revealed that the combination of C1q, C3b/C3i, C4b, C5, C5a, and MBL was associated with the best sensitivity (83.3%) and specificity (79.2%) for a cutoff value of 0.62 (likelihood ratio: 4.0; area under the curve: 0.853). Nevertheless, only a combined model showed acceptable results. The expression patterns of the complement factors suggested that PJI activates all three pathways of the complement system.

scholarly journals Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 199
Author(s):  
Urara Tanaka ◽  
Shunichi Kajioka ◽  
Livia S. Finoti ◽  
Daniela B. Palioto ◽  
Denis F. Kinane ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Resorption ◽  
Bone Loss ◽  
Inflammatory Cytokines ◽  
Osteoclast Differentiation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Bone Homeostasis ◽  
Osteoblastic Cell Line ◽  
Anti Inflammatory

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

scholarly journals Role of Synovial Exosomes in Osteoclast Differentiation in Inflammatory Arthritis

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 120
Author(s):  
Ji Eun Song ◽  
Ji Soo Kim ◽  
Ji Hye Shin ◽  
Ki Won Moon ◽  
Jin Kyun Park ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Inflammatory Arthritis ◽  
Mononuclear Cells ◽  
Osteoclast Differentiation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Healthy Donors ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of inflammatory arthritis. Exosomes isolated from synovial fluid of rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, and osteoarthritis (OA) patients were co-incubated with CD14+ mononuclear cells from healthy donors without macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclast differentiation was evaluated via tartrate-resistant acid phosphatase (TRAP) staining and activity and F-actin ring formation. RANKL expression on synovial exosomes was assessed using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Synovial exosomes were the lowest in OA patients; these induced osteoclastogenesis in the absence of M-CSF and RANKL. Osteoclastogenesis was significantly higher with more exosomes in RA (p = 0.030) than in OA patients, but not in AS or gout patients. On treating macrophages with a specified number of synovial exosomes from RA/AS patients, exosomes induced greater osteoclastogenesis in RA than in AS patients. Synovial exosomal RANKL levels were significantly higher in RA (p = 0.035) than in AS patients. Synovial exosome numbers vary with the type of inflammatory arthritis. Synovial exosomes from RA patients may bear the disease-specific “synovial signature of osteoclastogenesis.”

Synovial Fluid Biomarkers for the Diagnosis of Periprosthetic Joint Infection

2017 ◽  
Vol 99 (24) ◽  
pp. 2077-2084 ◽  
Author(s):  
Yong Seuk Lee ◽  
Kyung-Hoi Koo ◽  
Hyun Jung Kim ◽  
Shaoqi Tian ◽  
Tae-Young Kim ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Periprosthetic Joint Infection ◽  
Joint Infection

Synovial Fluid Alpha-Defensin Is an Adjunctive Tool in the Equivocal Diagnosis of Periprosthetic Joint Infection

2018 ◽  
Vol 33 (11) ◽  
pp. 3537-3540 ◽  
Author(s):  
Mick P. Kelly ◽  
Brian Darrith ◽  
Charles P. Hannon ◽  
Denis Nam ◽  
P. Maxwell Courtney ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Periprosthetic Joint Infection ◽  
Joint Infection

Effect of Icariin on Osteoclasts and Its Mechanism

2020 ◽  
Vol 10 (12) ◽  
pp. 1807-1812
Author(s):  
Xiaoxiao Wu ◽  
Xi Fu ◽  
Xiabing Qin
Keyword(s):  
Transcription Factors ◽  
Bone Resorption ◽  
Bone Loss ◽  
Mapk Pathway ◽  
Early Stage ◽  
Osteoclast Differentiation ◽  
Mapk Signaling ◽  
Therapeutic Drug ◽  
Actin Ring ◽  
B Subunit

Background: The paper aimed to elucidate the molecular mechanism of Icariin regulating RANKLinduced osteoclast-ogenesis and bone resorption, and to investigate whether Icariin could be a potential therapeutic drug for diseases of bone loss related to osteoclast. Material and methods: Osteoclasts were cultured. MTT to determine cell viability. Von Kossa to determine the effect of Icariin on bone resorption. F-actin ring staining to measure the expressions of various proteins, and WB method was used to measure the expression of p-65. Results: MTT showed that Icariin is not toxic to osteoclasts. The bone resorption result showed that RANKL-mediated osteoclast bone resorption was reduced in the early stage, and the higher the intervention concentration, the smaller the bone resorption area. F-actin ring staining indicated that it is possible to reduce the differentiation and bone resorption capacity of osteoclasts by hindering the formation of F-actin ring in the early stage, and in a concentration-dependentmanner. Significantly reduced the expressions of key transcription factors-NFATc1 and c-Fos. It significantly inhibited the phosphorylation and nucleation of NF-κB subunit p65 induced by RANKL, and significantly inhibited the phosphorylation of ERK and p38 proteins in the MAPK pathway activated by RANKL. Conclusion: Icariin can effectively inhibit osteoclast differentiation, F-actin ring formation, and bone resorption. By inhibiting the key transcription factors NFATc1 and c-Fos to down-regulate related expressions, thereby impeding osteoclast differentiation, Icariin may regulate key transcription factors NFATc1 and c-Fos through NF-κB and MAPK signaling pathways. Studies have suggested that Icariin could be a potential treatment for diseases of bone loss related to osteoclasts.

scholarly journals Metal on Metal Bearing in Total Hip Arthroplasty and Its Impact on Synovial Cell Count

2020 ◽  
Vol 9 (10) ◽  
pp. 3349
Author(s):  
Henrik C. Bäcker ◽  
Chia H. Wu ◽  
David Krüger ◽  
Clemens Gwinner ◽  
Carsten Perka ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Control Group ◽  
Total Hip ◽  
Metal On Metal ◽  
Matching Criteria ◽  
The Impact

Introduction: The effect of different bearings on synovial white blood cell (WBC) count and polymorphonuclear percentage (PMN%) in aspirations remains unclear. Therefore, this study investigates the impact of aseptic Metal-on-Metal (MoM) bearing on synovial fluid. Methods: We searched our arthroplasty registry for aseptic painful THAs with MoM bearings between 2011 and 2018. Then, a case-matched control group was selected with septic and aseptic Total Hip Arthroplasty (THA) with ceramic on a polyethylene (PE) bearing. The matching criteria consisted of gender, age +/−10 years, and time of aspiration (+/−2years). Periprosthetic Joint Infection (PJI) was defined according to the Infectious Diseases Society of America (IDSA), and Musculoskeletal Infection Society (MSIS) using bacterial cultures, sonication and histology. Results: In total, 19 patients who underwent hip aspiration with MoM bearing were identified. Five patients had to be excluded due to insufficient synovial fluid obtained (n = 2) or bacterial growth after sonication that was initially negative with the standard microbiological cultures (n = 3). As such, 14 were included. These patients were matched with 14 aseptic and 14 septic THAs with ceramic on a PE bearing, which constituted the control group. The mean serum chrome level was 20.0 ± 15.5 nmol/L and cobalt level 18.4 ± 22.1 nmol/L. The synovial WBC and PMN% varied significantly between MoM bearing group and the aseptic THA ceramic PE group (both p < 0.001), as well as the septic THA group (WBC p = 0.016, PMN% p < 0.001). Furthermore, the septic THA group had significantly higher CRP values than the aseptic MoM group (p = 0.016). Conclusion: MoM bearing shows significantly higher synovial WBC and PMN% when compared to aseptic THA with ceramic on PE bearing above the MSIS cut-off. This is an important consideration when diagnosing periprosthetic joint infection using the MSIS guidelines.

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