scholarly journals The expression of Netrin-1 in the MIA-induced osteoarthritic temporomandibular joint in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mian Xiao ◽  
Zhihui Hu ◽  
Henghua Jiang ◽  
Cheng Li ◽  
Huilin Guo ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Subchondral Bone ◽  
Osteoclast Differentiation ◽  
Structural Disorder ◽  
Temporomandibular Joint Disorders ◽  
Enzyme Linked Immunosorbent Assay ◽  
Micro Ct ◽  
Withdrawal Threshold ◽  
Important Regulator

AbstractSubchondral bone degeneration is the main pathological change during temporomandibular joint (TMJ) osteoarthritis (OA) development. Netrin-1, an axon-guiding factor, might play roles in OA development and pain. The purpose of this study was to investigate the expression of Netrin-1 in TMJ OA and its possible role in the progression of TMJ OA and pain. The synovial fluids of temporomandibular joint disorders (TMDs) patients were collected for Netrin-1 by enzyme linked immunosorbent assay (ELISA). TMJ OA model was built by MIA joint injection, and then the von Frey test, hematoxylin & eosin (H&E) staining, toluidine blue (TB) staining, immunohistochemical (IHC) staining and micro-CT were performed. After induction of osteoclast differentiation of raw264.7 cells, immunofluorescence (IF) was used to detect the Netrin-1 and its receptors on osteoclast membrane. The concentration of Netrin-1 increased in the synovial fluid of TMJ OA patients. After MIA injection to TMJ, the head withdrawal threshold (HWT) was significantly decreased. Microscopically, the structural disorder of subchondral bone was the most obvious at the 2nd week after MIA injection. In addition, Netrin-1 expression increased in the subchondral bone at the 2nd week after MIA injection. In vitro, the expressions of Netrin-1 and its receptor Unc5B were upregulated on the osteoclast membrane. Netrin-1 might be an important regulator during bone degeneration and pain in the process of TMJ OA.

scholarly journals Metabolic Syndrome Predisposes to Osteoarthritis: Lessons from Model System

Cartilage ◽  
2020 ◽  
pp. 194760352098016
Author(s):  
Sampath Samuel Joshua Pragasam ◽  
Vijayalakshmi Venkatesan
Keyword(s):  
Subchondral Bone ◽  
Fat Mass ◽  
Articular Chondrocytes ◽  
Bone Cyst ◽  
Primary Cultures ◽  
Abdominal Circumference ◽  
Enzyme Linked Immunosorbent Assay ◽  
Micro Ct ◽  
Tnf Α ◽  
And Cartilage

Objective The present study aims to assess for temporal changes in tibial subchondral bone and cartilage in WNIN/Gr-Ob rats (portraying obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, hypertension) in comparison with Wistar controls (WNIN) using anthropometry, micro-computed tomography (micro-CT), scanning electron microscopy (SEM), histopathology, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Design Body weight, abdominal circumference, body mass index (BMI), lean/fat mass, serum tumor necrosis factor (TNF)-α levels were measured (ELISA), followed by ultrastructural analysis of tibial subchondral bone (micro-CT) and cartilage architecture (histopathology and SEM) in WNIN/Gr-Ob and WNIN rats with age (3, 6 and 9 months). Additionally, primary cultures of articular chondrocytes isolated from 6-month-old WNIN/Gr-Ob and WNIN rats were assessed for matrix metalloproteinase (MMP)-13 and Collagen type II (COL2A1) by immunofluorescence. Results WNIN/Gr-Ob rats exhibited frank obesity with increased BMI, lean and fat mass vis-à-vis significantly higher levels of serum TNF-α (6>9>3 months) as compared with the controls. With an increase in BMI, WNIN/Gr-Ob rats presented with tibial cartilage fibrillation, erosion, osteophyte formation (6 months) and subchondral bone cyst (9 months) confirmed by histology and SEM. An increase in subchondral trabecular bone volume (sclerosis with decreased plate porosity) was observed in all ages in WNIN/Gr-Ob rats compared to their Control. Gaining insights, primary cultures of articular chondrocytes complemented with altered cellular expressions of COL2A1 and MMP-13 from WNIN/Gr-Ob rats, indicating osteoarthritis (OA) progression. Conclusion Multiple metabolic perturbations featured in WNIN/Gr-Ob rats were effective to induce spontaneous OA-like degenerative changes affecting knee joints akin to human OA.

scholarly journals Bushenhuoxue formula inhibits osteoclastogenesis and bone resorption on rabbit steroid-related osteonecrosis of the femoral head by suppressing NF-κB/NFATc1 pathway

2020 ◽  
Author(s):  
Peng Zhang ◽  
Songfeng Hu ◽  
Huihui Xu ◽  
Wenhua Yuan ◽  
Chenjie Xia ◽  
...  
Keyword(s):  
Femoral Head ◽  
Bone Resorption ◽  
Bearing Capacity ◽  
Weight Bearing ◽  
Enzyme Linked Immunosorbent Assay ◽  
Micro Ct ◽  
Model Group ◽  
Post Induction ◽  
Femoral Heads

Abstract Background: To investigate the effect and underlying mechanism of Bushenhuoxue formula (BSHXF) on steroid-related osteonecrosis of the femoral head (SONFH). Methods：Seventy-five male New Zealand white rabbits were divided into three groups: control group, model group and BSHXF group. Rabbit SONFH was induced by methylprednisolone (MPS) combined with lipopolysaccharide (LPS). At week 2 and 6 post induction, the corresponding number of rabbits were sacrificed, and the femoral heads were harvested for tissue analyses, including histopathology, mechanical test of femoral heads, micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry for p-P65 and co-staining of TRAP and alkaline phosphatase (ALP). Additionally, the serum TRACP5b level was measured using enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also evaluated the effect of BSHXF treatment on osteoclastogenesis in vitro. The protein level of cathepsin K (CTSK), P65, p-P65 and NFATc1 in rabbit femoral heads and RAW264.7 cells were detected, respectively.Results: At weeks 2 and 6 post induction, the elevated TRAP, p-P65 expression and reduced ALP expression were observed in the model group, with decreases in weight-bearing capacity of femoral heads and bone mass. After BSHXF treatment, the ratio of empty lacuna and the incidence of osteonecrosis in BSHXF group were markedly lower than that in model group. Micro-CT evaluation indicated that BSHXF has a preventive effect on bone loss in rabbit SONFH. In addition, BSHXF treatment increased weight-bearing capacity of femoral heads and reduced TRAP+ osteoclasts and serum TRACP5b level. Interestingly, CTSK, p-P65 and NFATc1 upregulation in necrotic femoral head could be reversed by BSHXF treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and down-regulated CTSK, p-P65 and NFATc1 expression in vitro.Conclusions: BSHXF could inhibit osteoclastogenesis and bone resorption on rabbit steroid-related osteonecrosis of the femoral head by suppressing NF-κB/NFATc1 pathway.

Comparison of the diagnostic accuracy of Ultrasonography and CBCT for detection of mandibular condyle erosion (an in-vitro study)

2021 ◽  
Vol 15 (5) ◽  
pp. 1661-1665
Author(s):  
Yasaman Kheirandish ◽  
Mehrdad Panjnoush ◽  
Shabnam Mohammed Charlie ◽  
Elham Romoozi
Keyword(s):  
Temporomandibular Joint ◽  
Mandibular Condyle ◽  
In Vitro Study ◽  
Temporomandibular Joint Disorders ◽  
The Body ◽  
Articular Disc ◽  
Mandibular Movement ◽  
Adequate Treatment ◽  
Bone Changes

Temporomandibular joint (TMJ) is one of the most important, unique and structurally has the highest complex synovial system in the body (1, 2). TMJ, encompassing the temporal bone, mandibular condyle and articular disc, is a diarthrodial joint. As a collective form, Temporomandibular Joint Disorders (TMD) is often with multifactorial etiologies, and these diseases can more commonly affect the soft-tissue components of the TMJ including the articular disc and posterior attachment, the osseous components of the TMJ and also the related muscles (3, 4). The most common cause of the regional orofacial pain of non-dental origin is a result of TMD. Additional symptoms may include TMJ sounds such as clicking, pumping, limited or asymmetric mandibular movement (5). As TMJ is covered by a layer of fibrocartilage, unlike other joints in the human body, the mandibular condyles can be damaged due to cartilage degeneration. In addition, arthritis can also be initiated because of the particular dynamics in the maxillofacial area (6). TMD's are frequently associated with degenerative bone changes which can involve the bone structures of the TMJ such as erosion, flattening, osteophytes, subchondral bone sclerosis and pseudocysts (7). To correctly diagnose the dysfunctions associated with the disease and for adequate treatment planning Knowledge about these bone changes is fundamental (8).

Melatonin Abates TMJOA Chronic Pain by MT2R in Trigeminal Ganglion Neurons

2021 ◽  
pp. 002203452110265
Author(s):  
W. Liu ◽  
H. Jiang ◽  
X. Liu ◽  
S. Hu ◽  
H. Li ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Temporomandibular Joint ◽  
Trigeminal Ganglion ◽  
Health Care Professionals ◽  
Analgesic Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Temporomandibular Joint Osteoarthritis ◽  
Monosodium Iodoacetate ◽  
Ganglion Neurons

Temporomandibular joint osteoarthritis (TMJOA) is one of the most common diseases causing chronic pain in the oral and maxillofacial region. So far, there are few ways to relieve the pain of TMJOA. Melatonin (MT) has a good analgesic effect in many diseases, including fibromyalgia, neuropathic pain, chronic headache, and burn pain, with very low acute toxicity and side effects. This study was to investigate the role and mechanism of MT in TMJOA chronic pain. In rats TMJOA chronic pain occurred at day 14 after an intra–temporomandibular joint injection of monosodium iodoacetate, which we previously reported. The enzyme-linked immunosorbent assay results showed that MT levels were higher in the synovial fluid from patients and rats with TMJOA as compared with those from control. Fluorescent retrograde tracing (Dil) identified that upregulation of MT type 2 receptor (MT2R) in trigeminal ganglion (TG) neurons innervating rat temporomandibular joints was accompanied by TMJOA chronic pain. Nociceptive behavior as assessed by von Frey and the Rat Grimace Scale demonstrated that exogenous administration of MT relieved chronic pain in TMJOA rats, whereas blocking MT2R with 4P-PDOT reversed the analgesic effect of MT. Immunofluorescence analysis also confirmed that MT inhibited CGRP and IB4 expression of TG neurons, and this inhibition was reversed by administering the MT2R antagonist in TMJOA rats. By using Fluo-3 AM-based calcium imaging in vitro, MT elicited calcium transients in Dil+ TG neurons, which were significantly abolished by 4P-PDOT. Collectively, this study suggested that MT relieves the TMJOA chronic pain of rats through downregulation of sensitized CGRP+ and IB4+ neurons in TG via MT2R. This will be helpful for health care professionals utilizing MT as an option against TMJOA chronic pain.

scholarly journals Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint

2021 ◽  
Author(s):  
Zhaoyichun Zhang ◽  
Lei Lu ◽  
Tao Ye ◽  
Shibin Yu ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Temporomandibular Joint ◽  
Subchondral Bone ◽  
Early Stage ◽  
Cartilage Degeneration ◽  
Pathological Feature ◽  
Semaphorin 4D ◽  
New Therapeutic Approaches

Subchondral bone loss is an important pathological feature of early-stage temporomandibular joint (TMJ) osteoarthritis (OA). Previous studies focused mainly on the bone resorption by osteoclasts in early-stage OA, but the bone formation feature has not drawn enough attention. Sema4D/Plexin-B1 is a pair of molecules expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblasts. The present study found that subchondral bone loss in early-stage TMJ OA was accompanied by up-regulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D level could inhibit the subchondral bone loss and cartilage degeneration of early-stage TMJ OA. In vitro, results revealed that Sema4D could reduce the expression of osteocalcin (OCN) and alkaline phosphatase (ALP), and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ OA might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in the early-stage OA holds promise as a strategy for new therapeutic approaches to osteoarthritis.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

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