Inflammatory Bone Research Articles

Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in oral squamous cell carcinoma cohort.

Chronic inflammation of the alveolar bones and connective tissues supporting teeth causes periodontal disease, one of the most prevalent infectious diseases in humans. It was previously reported that oral cancer was the sixth most common cancer in the world, followed by squamous cell carcinoma. Periodontal disease has been linked to an increased risk for oral cancer in some studies, and these studies have found a positive relationship between oral cancer and periodontal disease. In this work, we aimed to explore the potential correlation between oral squamous cell carcinoma (OSCC) and Periodontal disease. The single-cell RNA sequence analysis was applied to explore the genes that were closely associated with cancer-associated fibroblasts (CAFs). the head and neck squamous cell carcinoma. The Single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was applied to explore the scores of CAFs. Subsequently, the differentially expressed analysis was applied to explore the CAFs-related genes that play a key role in the OSCC cohort. The LASSO regression analysis and the COX regression analysis were applied to construct the CAFs-based periodontal disease-related risk model. In addition, the correlation analysis was used to explore the correlation between the risk model and clinical features, immune-related cells, and immune-related genes. By using the single-cell RNA sequence analysis, we successfully obtained the biomarkers for the CAFs. Finally, we successfully obtained a six-CAFs-related genes risk model. The ROC curve and survival analysis revealed that the risk model showed good predictive value in OSCC patients. Our analysis successfully provided a new direction for the treatment and prognosis of OSCC patients.

Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of the femoral head by regulating miR-200b-3p-mediated Wnt/β-catenin signaling pathway via inhibiting SP1 expression

BackgroundSteroid-induced osteonecrosis of the femoral head (SONFH) is the necrosis of the femur bone caused by prolonged and massive use of corticosteroids. The present study probed into the significance of Astragalus polysaccharide (APS) in SONFH progression.MethodsSONFH cell model was constructed using murine long bone osteocyte Y4 (MLO-Y4) cells and then treated with APS. mRNA microarray analysis selected differentially expressed genes between control group and SONFH group. RT-qPCR determined SP1 and miR-200b-3p expression. Levels of SP1, β-catenin, autophagy-related proteins (LC3II/LC3I, Beclin1, p62) and apoptosis-related proteins (Bax, C-caspase3, C-caspase9, Bcl-2) were tested by Western blot. ChIP and luciferase reporter assays confirmed relationship between SP1 and miR-200b-3p. Fluorescence intensity of LC3 in cells was detected by immunofluorescence. Flow cytometry assessed cell apoptosis. Osteonecrosis tissues from SONFH mice were examined by HE and TRAP staining.ResultsAPS induced autophagy and suppressed apoptosis in SONFH cell model. APS inhibited SP1 expression and SP1 overexpression reversed effects of APS on SONFH cell model. Mechanistically, SP1 targeted miR-200b-3p to inhibit Wnt/β-catenin pathway. MiR-200b-3p depletion rescued the promoting effect of SP1 on SONFH cell model by activating Wnt/β-catenin pathway. HE staining showed that APS treatment reduced the empty lacunae and alleviated inflammation in trabecular bone of SONFH mice. TRAP staining revealed decreased osteoclasts number in SONFH mice after APS treatment.ConclusionAPS regulated osteocyte autophagy and apoptosis via SP1/miR-200b-3p axis and activated Wnt/β-catenin signaling, thereby alleviating SONFH, shedding new insights for therapy of SONFH.

A COX-2 Inhibitor Does Not Interfere With the Bone-Protective Effects of Loading in Male Mice With Arthritis.

Mechanical loading enhances bone strength and counteracts arthritis-induced inflammation-mediated bone loss in female mice. It is unknown whether nonsteroidal anti-inflammatory drugs (NSAIDs; eg, COX-2 inhibitors) can reduce inflammation without affecting the loading-associated bone formation in male mice. The aim of this study was to investigate if loading combined with a COX-2 inhibitor (NS-398) could prevent arthritis-induced bone loss and inflammation in male mice. Four-month-old male C57BL/6J mice were subjected to axial tibial mechanical loading three times/week for 2 weeks. Local mono-arthritis was induced with a systemic injection of methylated bovine serum albumin on the first day of loading, followed by a local injection in one knee 1 week later. The arthritis induction, knee swelling, bone architecture, and osteoclast number were evaluated in the hind limbs. C-terminal cross-links as a marker for osteoclast activity was measured in serum. Compared with loading and arthritis alone, loading of the arthritic joint enhanced swelling that was partly counteracted by NS-398. Loading of the arthritic joint enhanced synovitis and articular cartilage damage compared with loading alone. Loading increased cortical bone and counteracted the arthritis-induced decrease in epiphyseal bone. NS-398 did not alter the bone-protective effects of loading. C-terminal cross-links, a bone resorption marker, was increased by arthritis but not loading. In conclusion, loading prevented arthritis-induced epiphyseal and metaphyseal bone loss, and NS-398 reduced knee swelling without affecting the bone-protective effects of loading. If our results can be extrapolated to the human situation, specific COX-2 inhibitors could be used in combination with loading exercise to prevent pain and swelling of the joint without influencing the bone-protective effects of loading. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Cryptococcus neoformans osteomyelitis of the tibia: a case report and review of the literature

IntroductionOsteomyelitis is a bone inflammation that can be related to various infectious agents. As with any other type of inflammation, the prevailing symptoms and signs may include redness, swelling, pain, and heat. Fungal osteomyelitis is rare and usually found in immune-compromised patients.Case presentationA non-human immunodeficiency virus immunocompromised Greek female patient, 82 years old, visited the emergency department due to a 3 day pain located mainly over the left tibia’s anterior surface, accompanied by swelling and redness. There was also a subcutaneous lesion of her left breast. Medical history revealed that the patient had an unmasked close contact with pigeons, a main host of the disease. Initial x-ray imaging showed an osteolytic area in the upper third of the tibial diaphysis. The patient was admitted and underwent a computed tomography-guided biopsy. The specimen revealed a Cryptococcus neoformans infection of the bone and the breast. She was treated with 400 mg fluconazole twice a day for 3 weeks while in hospital and 200 mg twice a day upon discharge for 9 months. After that, she underwent surgical debridement because of lasting local irritation. She was closely monitored in our outpatient office, and in her last visit, 1 year after the initial admission, inflammatory signs had regressed vastly.ConclusionsTo our knowledge, this is the ninth cryptococcal osteomyelitis of the tibia to be recorded since 1974, and the most unusual finding was the bifocal nature of the infection, affecting both the tibia and the breast.

Association of miR-21-5p with routine biochemical markers and inflammatory cytokines in hemodialysis patients

BackgroundAlthough the role of miR-21-5p in some kidney diseases is relatively documented, the relationship of miR-21-5p with markers of bone metabolism and inflammation in patients receiving hemodialysis (HD) remains unclear. Here, we aim to explore the relationship of miR-21-5p with routine biochemical parameters, mineral bone disorders, and inflammatory markers in HD patients. MethodsSerum miR-21-5p expressions from 60 HD patients and 20 healthy controls were analyzed with qPCR. Bone metabolism-related parameters such as receptor activator of nuclear factor-kappa B ligand (RANKL), osteocalcin, calcium, phosphorus, and parathormone; inflammation-related markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, and C-reactive protein (CRP); and oxidative stress markers such as total antioxidant status (TAS) and total oxidant status (TOS) were measured in serum samples of HD patients. ResultsWe showed for the first time that miR-21-5p expressions were increased in patients receiving HD. In addition, miR-21-5p expressions showed a significantly positive correlation with bone metabolism markers, i.e. RANKL, osteocalcin, phosphorus, and parathormone, and inflammation markers, i.e. TNF-α, IL-6, and CRP. We detected that areas under the receiver operating characteristic curve for miR-21-5p, RANKL, osteocalcin, TNF-a, IL-6, and oxidative stress index in HD patients were 0.9317, 0.7742, 0.9038, 0.7319, 0.7063, and 0.7738, respectively. ConclusionElevated miR-21-5p expressions are associated with routine biochemical and inflammatory markers in HD patients, suggesting that miR-21-5p might have diagnostic and/or therapeutic importance in the treatment of chronic kidney diseases.

Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.

Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens Clostridium sensu stricto, Bacteroides, and Intestinibacter was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera Collinsella, Megasphaera, Agathobaculum, Mediterraneibacter, Clostridium XIV, and Dorea, were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including Limosilactobacillus, were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. IMPORTANCE Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.

Study on the correlation between mineral bone metabolism and CRP in patients with SHPT during perioperative period.

This study mainly observes changes in perioperative mineral bone metabolism-related indicators and inflammatory factors in patients with secondary hyperparathyroidism (SHPT), and analyzed the correlation between mineral bone metabolism-related indicators and inflammatory factors. Clinical data were collected. The study detects mineral bone metabolism-related indicators and inflammatory factor of perioperative patients with SHPT before and 4 days after operation. The production of high-sensitivity c-reactive protein (hs-CRP) in human hepatocytes cells (LO2 cells) stimulated by different concentrations of parathyroid hormone-associated protein was detected by enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction(RT-PCR), and western blot. The levels of mineral bone metabolism-related indicators and hs-CRP in SHPT group were significantly higher than those of control group. After operation, serum calcium, serum phosphorus, iPTH, FGF-23 decreased, and the level of osteoblast active biomarkers increased, while the level of osteoclast active biomarkers decreased. The levels of hs-CRP decreased significantly after operation. With the increase of PTHrP concentration, hs-CRP level in supernatant of LO2 cells decreased first and then increased. RT-PCR and western blot shows the same trend. Parathyroidectomy can significantly improve bone resorption and inflammation in SHPT patients. We speculate that there may be an optimal range of PTH concentrations to minimize inflammation in the body.

Synergistic Effects of Combined Concurrent Training and Eri-Polyunsaturated Fatty Acid Supplementation on Bone Mineral Density, Muscle Strength, and Inflammation.

Obesity has been associated with lower bone mineral density (BMD) and rapid muscle weakness. Regular exercise and polyunsaturated fatty acid (PUFA) consumption have been recognized as nonpharmaceutical approaches to increase BMD and ameliorate muscle weakness. This study aimed to determine the effects of concurrent training (CCT) and Eri-PUFA supplementation on BMD, muscular strength, and inflammation in obese adults. A total of 33 obese participants were randomly assigned to one of three groups (n=11 per group): (1) a placebo group; (2) an Eri-PUFA ingestion group (ERI); or (3) a CCT and Eri-PUFA ingestion group (CCT+ERI). The ERI and CCT+ERI groups received approximately 2.5 g of linolenic acid per day from Eri silkworm pupae. The exercise program included aerobic and resistance exercises performed under supervision three times per week for 8 weeks. Before and after the 8-week intervention, BMD, muscular strength, and inflammatory markers were measured. Only the CCT+ERI group showed a significant increase in lumbar spine BMD (5.1%, P<0.01) and upper-body muscle strength (16.9%, P<0.01) after the intervention, with differences between the groups. After the intervention, both the ERI and CCT+ERI groups showed a significant decrease in the monocyte-to-lymphocyte ratio (-25%, P<0.01 and -21.4%, P<0.05, respectively) and tumor necrosis factor-alpha (-21.6%, P<0.05 and -19.4%, P<0.05, respectively). These findings demonstrate that combining CCT and Eri-PUFA supplementation increases BMD and upper-body muscular strength and decreases inflammation. Although Eri-PUFA consumption did not affect BMD or muscle strength directly, it may have an additive effect on BMD by reducing inflammation.

A New Mass Spectroscopy-Based Method for Assessing the Periodontal–Endodontic Interface after Intracanal Placement of Biomaterials In Vitro

Optimizing the interface between biomaterials and dental hard tissues can prevent leakage of bacteria or inflammatory mediators into periapical tissues and thus avoid alveolar bone inflammation. In this study, an analysis system for testing the periodontal-endodontic interface using gas leakage and subsequent mass spectrometry was developed and validated using the roots of 15 single-rooted teeth in four groups: (I) roots without root canal filling, (II) roots with an inserted gutta-percha post without sealer, (III) roots with gutta-percha post and sealer, (IV) roots filled with sealer only, and (V) adhesively covered roots. Helium was used as the test gas, and its leakage rate was found by measuring the rising ion current using mass spectrometry. This system made it possible to differentiate between the leakage rates of tooth specimens with different fillings. Roots without filling showed the highest leakage values (p < 0.05). Specimens with a gutta-percha post without sealer showed statistically significantly higher leakage values than groups with a filling of gutta-percha and sealer or sealer alone (p < 0.05). This study shows that a standardized analysis system can be developed for periodontal-endodontic interfaces to prevent biomaterials and tissue degradation products from affecting the surrounding alveolar bone tissue.

Vitamin D from UV-Irradiated Mushrooms as a Way for Vitamin D Supplementation: A Systematic Review on Classic and Nonclassic Effects in Human and Animal Models.

Recent literature has shown that vitamin D, in addition to its well-known activity on the skeleton, has many positive effects on health. Unfortunately, it is not easy to meet intake needs solely with food. Mushrooms could provide a valid way to achieve this goal, because they are one of the few sources of vitamin D. The aim of this systematic review was to summarize what has been reported in the literature on the treatment of animal and human models with irradiated commercial mushrooms, with particular attention paid to the effects on clinical outcomes associated with the classical and nonclassical vitamin D functions. A total of 18 articles were selected. Six studies were conducted on human samples, while twelve were focused on animal models. The six studies conducted in humans involved a large number of subjects (663), but the treatment period was relatively short (1-6 months). Furthermore, the treatment dosage was different in the various groups (600-3800 IU/day). Probably for this reason, the studies did not demonstrate clinical efficacy on the parameters evaluated (cognitive functions, muscle system/function, metabolic syndrome). Indeed, those studies demonstrated an efficacy in increasing the blood levels of 25(OH)D2, but not in increasing the levels of 25(OH)D total. In 9 of 12 studies conducted on the animal model, however, a clinical efficacy on bone metabolism, inflammation, and cognitive performance was demonstrated. The results of this systematic review indicate that the intake of vitamin D from irradiated mushrooms could possibly help to meet vitamin D needs, but the dosage and the time of treatment tested need to be evaluated. Therefore, studies conducted in humans for longer periods than the studies carried out up to now are necessary, with defined dosages, in order to also evaluate the clinical efficacy demonstrated in animal models both for the classical (bone metabolism) and nonclassical (muscle function, cognitive performance, anti-inflammatory, and antioxidant activities) effects of vitamin D.

Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort.

Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that mainly involves children and adolescents. The association with other inflammatory disorders, such as inflammatory bowel disease (IBD), psoriasis, and arthritis, has been reported in the literature. In particular, the relationship between bone and intestinal inflammation is still poorly understood. For this purpose, our review aims to describe the cases reported in the literature concerning this association and to compare them with data from our single-center cohort of patients. We conducted a literature review of published cases of CNO associated with IBD. Eligible articles were identified through a Medline search in the PubMed database until December 2022. We retrospectively reviewed medical records of patients with CNO referred to G. Pini Hospital and compared them with the literature-review-based cohort. Fifty-seven patients with a defined diagnosis of CNO and associated IBD were described in the literature (female 55%). The median age of onset of the disease (CNO or IBD) was 11 years. In 32/53 (60%), a diagnosis of Crohn's disease (CD) was made, while 18 (34%) patients were classified as suffering from ulcerative colitis (UC) and 3 (6%) from undifferentiated IBD. The diagnosis of CNO preceded the diagnosis of IBD in 59% of cases; while in 24%, IBD anticipated CNO; and in 17%, the two conditions appeared simultaneously. The median time between the two events was 24 months. In our Italian cohort (n = 23 patients), no diagnosis of IBD was made. No significant differences were found when comparing clinical and demographical characteristics of the Italian vs. review-based cohort, except for a significant involvement of rachis in the Italian group. The correlation between autoinflammatory bone disease and intestinal inflammation should be further investigated. It is essential to promote awareness among pediatric rheumatologists and gastroenterologists about this possible association to facilitate the diagnosis and better optimize treatment.

The Impact of Osteitis on Quality of Life in Patients with Chronic Rhinosinusitis.

Introduction: Chronic rhinosinusitis (CRS) is a significant health problem worldwide with an estimated prevalence of 5-12% in the general population. Osteitis refers to inflammation of bone characterized by bone remodeling, neo-osteogenesis and thickening of adjacent mucosa. These changes are evidenced by specific radiological appearance on Computerized Tomography (CT) which may be localized or diffuse dependent on extent of disease. Osteitis act as a marker of severity in chronic rhinosinusitis and can significantly affect the patient's Quality of Life (QOL) proportional to its severity. Aim: To analyze the impact of osteitis on quality of life in patients with chronic rhinosinusitis as evidenced by pre-operative Sinonasal Outcome Test-22(SNOT-22) scores. Materials & Methods: 31 patients diagnosed to have chronic rhinosinusitis with co-existing osteitis were enrolled in this study based on computerized tomography scan Paranasal Sinuses (PNS) findings and graded as per the calculated Global Osteitis Scoring Scale. Accordingly, patients were categorised into those without significant osteitis, with mild, moderate and severe osteitis. Baseline quality of life in these patients was assessed using the Sinonasal Outcome Test-22 (SNOT-22) and its association with the severity of osteitis analysed.Results: There is a very strong correlation between severity of osteitis and quality of life in the study population based on the Sinonasal Outcome Test-22 scores (p = 0.000). The mean Global Osteitis score was 21.65 with standard deviation 5.66. Maximum score obtained was 38 and minimum score 14.Conclusion: • Osteitis has a significant impact on quality of life in patients with chronic rhinosinusitis. • Severity of osteitis has a direct relation to quality of life in chronic rhinosinusitis.

Педіатричні аспекти гострого гематогенного остеомієліту в дитини раннього віку: клінічний випадок

Acute hematogenous osteomyelitis is one of the common bacterial infections in children of early age, which is accompanied by mild symptoms at the initial stage of diagnosis. The onset of the disease is usually acute with fever, intoxication syndrome, focal signs of bone inflammation and limitation of limb function. Purpose - to show the features of diagnosis and treatment of acute hematogenous osteomyelitis in an infant based on clinical observation. Clinical case. The clinical case of a child of early age with acute hematogenous osteomyelitis, who was hospitalized with complaints of an increase in body temperature up to 40°C, restlessness, swelling and hyperemia of the lower part of the right thigh and right knee joint, and movement disorders in the right leg, was presented. The general condition of the child upon admission is severe due to intoxication, hyperthermic syndromes and local changes in the right lower limb, which was in a forced position, pronation. There were no active movements in the right leg, passives ones were painful. Rotational movements in the right leg are possible, but painful. The soft tissues in the area of the right hip and knee joints, as well as the thighs, were not changed in color, their swelling was noted. Conclusions. Symptoms of acute hematogenous osteomyelitis in young children are often nonspecific. Intoxication syndrome symptoms and local changes as movement disorders in the limb in children of this age group dominate. Pain can be detected during the examination, which is clearly localized with sensitivity over the infected bone; edema may be present. Changes of complete blood count are mild, while the determination of C-reactive protein during the initial evaluation can serve as a baseline value for sequential monitoring. The sensitivity of X-ray examination at the beginning of the disease is low, radiological changes appear only 7-21 days after infection. Empiric antimicrobial therapy aimed at Staphylococcus aureus should be prescribed immediately after the detection of acute hematogenous osteomyelitis clinical signs even before receiving results of additional research methods. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

LIPUS as a potential strategy for periodontitis treatment: A review of the mechanisms.

Periodontitis is a chronic inflammatory condition triggered by oral bacteria. A sustained inflammatory state in periodontitis could eventually destroy the alveolar bone. The key objective of periodontal therapy is to terminate the inflammatory process and reconstruct the periodontal tissues. The traditional Guided tissue regeneration (GTR) procedure has unstable results due to multiple factors such as the inflammatory environment, the immune response caused by the implant, and the operator's technique. Low-intensity pulsed ultrasound (LIPUS), as acoustic energy, transmits the mechanical signals to the target tissue to provide non-invasive physical stimulation. LIPUS has positive effects in promoting bone regeneration, soft-tissue regeneration, inflammation inhibition, and neuromodulation. LIPUS can maintain and regenerate alveolar bone during an inflammatory state by suppressing the expression of inflammatory factors. LIPUS also affects the cellular behavior of periodontal ligament cells (PDLCs), thereby protecting the regenerative potential of bone tissue in an inflammatory state. However, the underlying mechanisms of the LIPUS therapy are still yet to be summarized. The goal of this review is to outline the potential cellular and molecular mechanisms of periodontitis-related LIPUS therapy, as well as to explain how LIPUS manages to transmit mechanical stimulation into the signaling pathway to achieve inflammatory control and periodontal bone regeneration.

MiR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway.

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients.

The Role of Leptin and Adiponectin in Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disease, characterized by chronic synovial inflammation and destruction of cartilage and bone, results in varying degrees of deformity and functional disability. Previous research has shown that there is a link between adipokines and RA, but also other systemic diseases such as cardiovascular disease and diabetes mellitus. Adipokines are biologically active substances, which are predominantly or exclusively secreted from adipocytes of adipose tissue, or other adipose tissue cells such as: preadipocytes, immune cells infiltrated in AT, or other cell types within this tissue. These molecules play a significant role in energy homeostasis and metabolism regulation, and are also involved in chronic inflammation and metabolic dysfunctions. Some of the adipokines act like hormones in glucose homeostasis and appetite regulation, while others, like cytokines, support the link between obesity and insulin resistance with the immune system and the inflammatory process. However, the clear role of adipokines in pathological conditions has not yet been established. This review will focus on current knowledge about the role of the two most prominent adipokines, leptin and adiponectin, in the pathogenesis of RA.

Post-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation

Post-traumatic osteoarthritis (PTOA) develops secondary to a joint injury and accounts for 12 % of all osteoarthritis. These injuries, often of the lower extremity joints, occur due to trauma or accidents related to athletic or military activities. They primarily affect younger individuals although PTOA can occur across the spectrum of age. Pain and functional disability caused by PTOA confer a heavy economic toll on patients, in addition to detrimentally affecting their quality of life. Both high energy injuries that cause articular surface fracture with or without subchondral bone disruption and low-energy injuries involving joint dislocations or ligamentous injury cause PTOA, albeit through different mechanisms. Regardless, chondrocyte death, mitochondrial dysfunction, reactive oxygen species production, subchondral bone remodeling, inflammation and cytokine release in the cartilage and synovium play integral roles in the pathogenesis of PTOA. Evolving surgical methods are focused on stabilizing articular surface and joint structure congruity. However, to date there are no disease modifying medical therapies against PTOA. Increased recent understanding of the pathogenesis of the subchondral bone and synovial inflammation as well as that of chondrocyte mitochondrial dysfunction and apoptosis have led to the investigation of new therapeutics targeting these mechanisms to prevent or delay PTOA. This review discusses new advances in our understanding of cellular mechanisms underlying PTOA, and therapeutic approaches that are potentially effective in reducing the self-propagating cycle of subchondral bone alterations, inflammation, and cartilage degradation. Within this context, we focus therapeutic options involving anti-inflammatory and anti-apoptotic candidates that could prevent PTOA.

Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells.

The T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is widely expressed in the immune system but was initially identified as the lineage-specifying transcription factor of Th1 CD4+ T cells, where it governs expression of the signature cytokine IFN- γ and represses alternative cell fates like Th2 and Th17. T-bet's paralog Eomes is less abundantly expressed and Eomes+ CD4+ T cells are mostly found in the context of persistent antigen exposure, like bone marrow transplantation, chronic infection or inflammation as well as malignant disorders. However, it has remained unresolved whether Eomes executes similar transcriptional activities as T-bet in CD4+ T cells. Here we use a novel genetic approach to show that Eomes expression in CD4+ T cells drives a distinct transcriptional program that shows only partial overlap with T-bet. We found that Eomes is sufficient to induce the expression of the immunoregulatory cytokine IL-10 and, together with T-bet, promotes a cytotoxic effector profile, including Prf1, Gzmb, Gzmk, Nkg7 and Ccl5, while repressing alternative cell fates. Our results demonstrate that Eomes+ CD4+ T cells, which are often found in the context of chronic antigen stimulation, are likely to be a unique CD4+ T cell subset that limits inflammation and immunopathology as well as eliminates antigen-presenting and malignant cells.

IL-37 alleviates alveolar bone resorption and inflammatory response through the NF-κB/NLRP3 signaling pathway in male mice with periodontitis

ObjectivePeriodontitis is an inflammatory disease, characterized by periodontal pocket formation and alveolar bone resorption, is one of the most common oral diseases. Interleukin-37 (IL-37) is a novel inflammatory suppressor that plays an important role in many inflammatory diseases. This study aimed to investigate the role of IL-37 in periodontitis DesignA mouse model of periodontitis was established by Porphyromonas gingivalis. After four weeks treatment of recombinant human IL-37 (rhIL-37), the effects of IL-37 on the gingival index and tooth loosening degree of periodontitis mice were observed. H&E staining and micro-CT scanning were used to analyze the bone resorption of the maxillary. The number of osteoclasts was counted by TRAP staining and the differentiation of osteoclasts was evaluated by immunohistochemistry. The expression of inflammatory cytokines was detected by ELISA, and the protein expressions of the NF-κB/NLRP3 pathway were analyzed by WB. ResultsRhIL-37 significantly decreased the gingival index and tooth mobility degree, inhibited maxillary bone resorption, decreased the number of osteoclasts and the expression of calcitonin receptor (CTR), periodontal cathepsin K (CTSK) and receptor activator of NF-κB ligand (RANKL), and increased the expression of osteoprotegerin (OPG) in periodontitis mice. At the same time, rhIL-37 significantly decreased the expression of IL-1β, IL-6 and TNF-α, and increased the expression of IL-10 in the gingival tissue of periodontitis mice. In addition, rhIL-37 significantly inhibited the protein expressions of p-p65, NLRP3, ASC, caspase-1 and IL-1β in periodontitis mice. ConclusionIL-37 may alleviate alveolar bone resorption and inflammation response in periodontitis through the NF-κB/NLRP3 pathway.

Silica coated high performance oxide ceramics promote greater ossification than titanium implants: an in vivo study

BackgroundThis in vitro study investigated the osseointegration and implant integration of high performance oxide ceramics (HPOC) compared to titanium implants in rabbits.MethodsHistomorphometry was conducted around the distal, proximal, medial, and lateral aspects of the HPOC to quantify the amount of mature and immature ossification within the bone interface. Histomorphometry was conducted by a trained musculoskeletal pathologist. The region of interest (ROI) represented the percentage of surrounding area of the implant. The percentage of ROI covered by osteoid implant contact (OIC) and mature bone implant contact (BIC) were assessed. The surrounding presence of bone resorption, necrosis, and/or inflammation were quantitatively investigated.ResultsAll 34 rabbits survived the 6- and 12-week experimental period. All HPOC implants remained in situ. The mean weight difference from baseline was + 647.7 mg (P < 0.0001). The overall OIC of the ceramic group was greater at 6 weeks compared to the titanium implants (P = 0.003). The other endpoints of interest were similar between the two implants at all follow-up points. No difference was found in BIC at 6- and 12-weeks follow-up. No bone necrosis, resorption, or inflammation were observed.ConclusionHPOC implants demonstrated a greater osteoid implant contact at 6 weeks compared to the titanium implants, with no difference found at 12 weeks. The percentage of bone implant contact of HPOC implants was similar to that promoted by titanium implants.