Receptor Activator Of Nuclear Factor kappa-B Ligand Levels Research Articles

Effect of low-intensity laser therapy on levels of biomarkers during orthodontic tooth movement – A systematic review

This systematic review aimed to explore the association between low-intensity laser therapy (LILT) and various biomarkers, elucidating the potential of this therapeutic modality to expedite orthodontic tooth movement (OTM). A systematic literature search was conducted using electronic databases including PubMed, Central of the Cochrane Library, and Google Scholar databases. Randomized controlled trials (RCTs) and non-randomized controlled clinical trials (nRCTs) using LILT as an adjunct to the standard orthodontic procedures in human and animal subjects as participants were included in the study. The quality of the human and animal studies was assessed using the Revised Cochrane risk of bias tool and Systematic Review Centre for Laboratory Animal Experimentation’s (SYRCLE’s) risk of bias tool respectively. Animal studies revealed increased receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL), matrix metalloproteinase-9 (MMP-9), and collagen type I expression. Human studies showed elevated interleukin-1-beta (IL-1β), interleukin-16 (IL-16) and RANKL levels, suggesting LILT influences biomarkers associated with bone resorption and connective tissue rearrangement. A high risk of bias was observed in all animal studies and 5 out of 6 human studies. The systematic review concluded that LILT emerges as a promising technique for enhancing orthodontic tooth movement, influencing key biomarkers linked to osteoclastic activity and collagen synthesis. However, the high risk of bias in animal and human studies emphasizes the need for further research to validate findings and optimize laser parameters for clinical benefits.

Systemic Melatonin Supplementation as an Adjunct to Non-Surgical Periodontal Treatment in Obese Patients with Periodontitis

Background: Obesity is considered an important risk factor for periodontal disease. It has been reported that reactive oxygen species linking both diseases, systemic melatonin supplementation as antioxidant therapy, was addressed as an adjuvant to scaling and root surface debridement (SRP) to enhance the treatment of periodontitis. Objective: To investigate the efficacy of systemic melatonin administration in periodontitis-obese patients as an adjuvant to scaling and root surface debridement (SRP). Methods: A randomized clinical trial was conducted at a dental-specialized center. Eighty subjects were included and allocated into group-I: twenty periodontium-healthy, normal-weight people; group-II: 30 obese patients with stage-III treated only with SRP; and group-III: 30 obese patients with stage-III periodontitis treated with SRP and 5mg melatonin. periodontitis and subjected to estimation, serum levels of Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL) were estimated in all groups. Probing pocket depth (PPD), bleeding on probing (BOP), and relative attachment level (RAL) were estimated in Groups II and III at baseline and after a one-month visit. Results: RANKL baseline visits were significantly different between the control and studied groups, with no significant difference in clinical parameters except for PPD. The 2nd visit showed a significant difference in BOP score-1 compared to RAL and BOP score 0. In the second visit, only weak negative and positive significant correlations were found between RANKL and BOP. Conclusion: Daily use of 5 mg of melatonin improves periodontal parameters and decreases serum RANKL levels.

Inflammation is responsible for systemic bone loss in patients with seropositive rheumatoid arthritis treated with rituximab.

We investigated the effect of rituximab on systemic bone metabolism in patients with seropositive rheumatoid arthritis (RA). Twenty seropositive patients with RA were enrolled and administered one cycle of rituximab. If RA became active for > 6 months after the first rituximab cycle, a second cycle was initiated; otherwise, no additional treatment was administered. Patients were divided into two groups according to the number of rituximab treatment cycles. In patients treated with a second cycle, the total hip bone mineral density (BMD) was clinically low, whereas the serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) were increased at 12 months. BMD in patients treated with one cycle did not change at 12 months, whereas serum RANKL levels decreased at all time points. DAS28 activity improved in both groups from baseline to 4 months; however, from 4 to 12 months, DAS28 activity worsened in the develgroup with the second cycle but remained stable in the group with one cycle. Systemic inflammation, reflected by increased disease activity, may be responsible for the increase in RANKL levels, which causes systemic bone loss in rituximab-treated patients with RA. Although rituximab affects inflammation, it does not seem to alter systemic bone metabolism in RA.

The effect of vitamin D on the early clinical manifestations of menopausal syndrome and the production of cytokines, involved in bone remodeling

Introduction. The problem of early manifestations of menopausal syndrome is due to the high prevalence among postmenopausal women, a wide range of clinical manifestations, a sharp decrease in the quality of life, not always sufficient effectiveness of menopausal hormone therapy (MHT) in the presence of restrictions on its use.The aim. To evaluate the dynamics of clinical manifestations of menopausal syndrome and to determine the pathogenetic effects of vitamin D preparation when used in combination with menopausal hormone therapy in women of early postmenopausal age with menopausal syndrome.Materials and methods. 154 women were examined, of which 81 were characterized by the presence of clinical manifestations of menopausal syndrome. All women with menopausal syndrome received menopausal hormone therapy with estradiol and didrogesterone drug for 6 months, while 39 women additionally also took the vitamin D drug. Before and after therapy in patients with menopausal syndrome, the prevalence of symptoms of the Green scale was assessed. Concentrations of 25(OH) D, osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) were determined in the blood serum of all women.Results and discussion. The use of MHT by women with menopausal syndrome leads to a decrease in the frequency of registration of a number of symptoms of the Green scale (p < 0.05). At the same time, a decrease in the frequency of registration of individual complaints is found only in the group of women who, along with MYT, received a vitamin D preparation (p < 0.05). Taking the vitamin D preparation is accompanied by an increase in its initially reduced serum concentrations to normal values (p < 0.001). The addition of cholecalciferol to the complex therapy of menopausal syndrome ensures the normalization of RANKL levels by reducing its production in the dynamics of treatment (p < 0.05) A decrease in the concentration of RANKL in response to the complex intake of a hormonal drug and cholecalciferol caused higher OPG/RANKL index values in the basic group by the end of therapy than in women of the comparison group (p < 0.01).Conclusions. The obtained effects of vitamin D preparation when prescribed in combination with menopausal hormone therapy (reduction of the frequency of symptoms of menopausal syndrome, reduction of initially elevated levels of RANKL) indicate the expediency of its use in the treatment of early manifestations of menopausal syndrome.

The role of miR-433-3p in vascular calcification in type 2 diabetic patients: targeting WNT/β-Catenin and RANKL/RANK/OPG signaling pathways

BackgroundVascular calcification (VC) is a major predictor of cardiovascular diseases that represent the principal cause of mortality among type-2 diabetic patients. Accumulating data suggest the vital role of some microRNAs on vascular calcification as an epigenetic regulator. Thus, we assessed herein, the role of serum miR-433-3p in vascular calcification in type-2 diabetic patients.MethodsTwenty healthy subjects (control group) and forty diabetic patients (20 without VC and 20 with VC) were involved in the study. miR-433-3p gene expression was measured. Runx2, Dickkopf-1 (DKK1), β-catenin, Receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) levels in serum were assessed by ELISA technique.ResultsDiabetes patients had significantly lower levels of miR-433-3p expression in comparison to the control group, with the lowest levels being found in diabetic patients with VC. Furthermore, Runx2, β-catenin, and RANKL levels were significantly increased with concomitant lower DKK1 and OPG levels detected in the two diabetic groups especially those with VC.ConclusionCollectively, the study documented that down-regulation of miR-433-3p may contribute to the development of VC through activating WNT/β-Catenin and RANKL/RANK/OPG signaling pathways.

Interleukin-21 knockout reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis.

Estrogen deficiency accelerates osteoporosis in elderly women. However, the role of IL-21 in postmenopausal osteoporosis remains unclear. Female wild-type (WT) C57BL/6 and IL-21 knockout (KO) mice were used for ovariectomy (OVX). Here, IL-21 levels were significantly increased in the serum and bone tissues of WT-OVX mice. The trabecular bone space of the femur was significantly increased, and the bone mass was reduced in OVX mice, accompanied by a significant decrease in the maximum load, energy absorption, and elastic modulus indices. In contrast, IL-21 knockout effectively alleviated the effects of OVX on bone mass. Serum TRACP-5b and receptor activator of nuclear factor kappa B ligand (RANKL) levels and osteoclastogenesis were significantly higher in OVX mice than in sham mice, while serum TRACP-5b and RANKL levels and osteoclastogenesis were significantly decreased in IL-21 KO+OVX mice compared to WT+OVX mice. IL-21 knockdown reduces TRACP-5b, RANKL, and osteoclastogenesis, effectively preventing bone resorption and alleviating the progression of OVX-induced osteoporosis.

Cystic fibrosis related bone disease in children: Can it be predicted?

Cystic fibrosis (CF) -related bone disease (CFBD) is an important complication of CF, and low BMD in childhood is a precursor of CFBD. Here, we aimed to investigate bone turnover biomarkers, including osteocalcin (OC), receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in relation to low BMD in children with CF (cwCF). We also evaluated factors which could affect bone turnover with particular emphasis on fat-free mass (FFM), forced expiratory volume in 1s (FEV1), hand grip strength (HGS), and functional capacity and physical activity. Sixteen cwCF aged 8-18 years with moderate low BMD (group1) and 64 cwCF with normal BMD (group2) were enrolled. Serum RANKL, OC, and OPG were determined by immunoenzymatic assays. Multiple parameters including pancreatic status, lung functions, body mass index (BMI), FFM measured by bioelectric impedance analysis (BIA), 6-minute walk test, vitamin D, nutritional intake, HGS, functional capacity and physical activity, serum and urine biomarkers were compared between the two groups. We found similar serum levels of RANKL (p=0.501), OC (p=0.445), OPG (p=0.380), and RANKL/OPG ratio (p=0.449) between group1 and group2 in cwCF. BMI z-score (p<0.001), FFMI z-score (p<0.001), FEV1 z-score (p=0.007), and right-HGS (%pred) (p=0.009) significantly differed between the two groups. Multivariate linear regression revealed that the only factors that predicted BMD were FFMI z-score and HGS %pred. Serum OC, OPG, RANKL and RANKL/OPG ratio did not predict BMD in cwCF. FFMI z-score and HGS %pred measured by non-invasive and practical methods were the best predictors of BMD.

Pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases: systematic review and meta-analysis

BackgroundPro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity. However, evidence regarding the exact role of pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases is unclear. We aimed to execute a systematic review and meta-analysis about the pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors levels in peri-implant diseases.MethodsThe focused question was elaborated to summarize the levels of pro-and anti-inflammatory cytokines and osteoclastogenesis-related factors in tissue samples (mRNA) and biofluids (protein levels) of patients with/without peri-implant diseases. Electronic searches of the PubMed, Cochrane Controlled Trials Registry, Web of Science, EMBASE, Scopus and Google scholar databases were conducted for publications up to March 2023. Meta-analysis evaluating the mediator´s levels (protein levels by ELISA) in peri-implant crevicular fluid (PICF) were made. The effect size was estimated and reported as the mean difference. The 95% confidence interval was estimated for each mediator, and the pooled effect was determined significant if two-sided p-values < 0.05 were obtained.ResultsTwenty-two publications were included in the systematic review (qualitative analysis), with nine of these subjected to meta-analyses (quantitative analysis). In the qualitative analysis, higher pro-inflammatory cytokines [Interleukin (IL)-1β, IL-6] and pro-osteoclastogenic mediator [Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL)] levels were observed in PICF of individuals with peri-implant diseases in comparison to healthy individuals. Higher RANKL/osteoprotegerin (OPG) ratios were observed in PICF from individuals with peri-implant diseases in comparison to healthy individuals. Meta-analysis showed higher RANKL levels in diseased groups compared to controls.ConclusionsThe results showed that the levels of IL-1β, IL-6, IL-10, and RANKL/OPG are not balanced in peri-implant disease, suggesting that these mediators are involved in the host osteo-immunoinflammatory response related to peri-implantitis.

Comparative study of the synovial levels of RANKL and OPG in rheumatoid arthritis, spondyloarthritis and osteoarthritis

IntroductionIn chronic arthropathies, there are several mechanisms of joint destruction. In recent years, studies have reported the implication of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) in the process of activation and differentiation of osteoclasts, a key cell in the development of bone erosion. The RANKL/OPG ratio is increased in the serum of patients with malignant diseases and lytic bone disease, as well as rheumatoid arthritis (RA). The objective of this study was to measure and compare the concentrations of OPG and RANKL in the synovial fluid (SF) of patients with rheumatoid arthritis, spondyloarthritis (SpA) and osteoarthritis (OA).MethodsThis was an observational and cross-sectional study with 83 patients, 33 with RA, 32 with SpA and 18 with OA, followed up regularly in the outpatient clinics of the Rheumatology Department of the Clinics Hospital of the Ribeirão Preto Medical School-USP. All patients were assessed for indications for arthrocentesis by the attending physicians at the time of SF collection and were evaluated for demographic variables and medication use. Disease activity was assessed in individuals with RA and SpA. The quantification of SF OPG and RANKL levels was performed by ELISA, and the correlations of the results with clinical, laboratory and radiological parameters were assessed.ResultsWe found no statistically significant difference in the RANKL and OPG levels among the groups. Patients with RA showed a positive correlation between the SF cell count and RANKL level (r = 0.59; p < 0.05) and the RANKL/OPG ratio (r = 0.55; p < 0.05). Patients with OA showed a strong correlation between C-reactive protein (CRP) and the RANKL/OPG ratio (r = 0.82; p < 0.05). There was no correlation between the OPG and RANKL levels and markers of inflammatory activity or the disease activity index in patients with RA or SpA.ConclusionWithin this patient cohort, the RANKL/OPG ratio was correlated with the SF cell count in patients with RA and with serum CRP in patients with OA, which may suggest a relationship with active inflammation and more destructive joint disease.

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities.

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.

Role of denosumab in bone erosions in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and synovitis which evolve into joint destruction and deformity. Bone abnormalities are represented by marginal bone erosions and iuxta-articular and generalized osteoporosis. Overactivation of osteoclasts along with dysregulation of osteoblasts are the key events. Bone resorption is mediated by the receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANK-L), responsible for the differentiation, proliferation, and activation of osteoclasts. RANK-L binds its receptor RANK, localized on the surface of preosteoclasts and mature osteoclasts promoting osteoclastogenesis. High levels of RANK-L were demonstrated in active RA patients. Denosumab, a fully human monoclonal antibody, binds RANK-L and suppresses the RANK-RANK-L signaling pathway leading to the inhibition of osteoclastogenesis. A retrospective analysis of published studies such as clinical trials evidenced the efficacy of denosumab in preventing bone erosion progression in RA patients. Key messages Key questions to answer in future include the following: Could denosumab be associated with other biologic therapies in RA patients? Could denosumab block the progression of bone damage in RA? Could denosumab be used for the prevention of bone erosion in RA?

Serum OPG and RANKL Levels as Risk Factors for the Development of Cardiovascular Calcifications in End-Stage Renal Disease Patients in Hemodialysis

Cardiovascular calcifications (CVC) are frequently observed in chronic kidney disease (CKD) patients and contribute to their cardiovascular mortality. The aim of the present study was to investigate the impact of osteoprotegerin (OPG)/Receptor Activator of NF-κΒ (RANK)/RANK ligand (RANKL) pathway in the development and evolution of CVCs in hemodialysis patients. In total, 80 hemodialysis patients were assessed for the presence of vascular (abdominal aorta and muscular arteries) calcifications and results were correlated to serum OPG and RANKL levels and the OPG/RANKL ratio. Traditional cardiovascular risk factors and mineral bone disease parameters were also estimated. The presence of VCs was also evaluated 5 years after the initiation of the study, and results were correlated to the initial serum OPG levels. Age, diabetes mellitus, coronary artery disease and OPG levels (p < 0.001) were associated with VCs, whereas RANKL levels were not. Multivariate analysis though revealed that only OPG levels were significantly associated with abdominal aorta calcifications (p = 0.026), but they were not correlated with the progression of VCs. Serum OPG levels are positively and independently associated with VCs in HD patients, but not with their progression. RANKL levels did not show any associations, whereas further studies are needed to establish the significance of OPG/RANKL ratio.

Changes in RANKL and TRAcP 5b after discontinuation of denosumab suggest RANKL mediated formation of osteoclasts results in the increased bone resorption

The rapid increase in bone turnover occurring when discontinuing long-term treatment with denosumab (DMAB), an antibody that neutralizes receptor activator of nuclear factor kappa-B ligand (RANKL) is not fully understood. We aimed to investigate the mechanisms underlying the rebound activation of bone resorption by measuring tartrate-resistant acid phosphatase 5b (TRAcP 5b), RANKL, osteoprotegerin (OPG), C-terminal collagen crosslinks (CTX), and procollagen type I N-propeptide (P1NP) in patients discontinuing long-term DMAB. Sixty-one patients with BMD T-score > - 2.5 at the spine and hip discontinuing long-term DMAB were randomized to treatment with zoledronate (ZOL) 6months (6M group, n = 20), 9months (9M group, n = 20) or 12months after the last DMAB injection or when bone turnover was high (12M group, n = 21). Bone turnover markers were measured immediately before initiation of ZOL treatment. We found higher CTX and PINP in the 9M and 12M groups compared to the 6M group (p < 0.001). In the 6M group, TRAcP 5b was lower and RANKL higher than in the other two groups (p < 0.001). TRAcP 5b correlated negatively with RANKL (R = - 0.54), and time since the last DMAB injection correlated positively with CTX (R = 0.56), PINP (R = 0.72), TRAcP 5b (R = 0.51) and negatively with RANKL (R = - 0.70) (p < 0.001 for all). We found no difference in OPG between groups. Following discontinuation of long-term DMAB, we find high levels of RANKL, which most likely result in an increase in the number of active osteoclasts (illustrated by TRAcP5b) causing an increased bone turnover.

Differential Recovery Patterns of the Maxilla and Mandible after Eliminating Nasal Obstruction in Growing Rats.

Although nasal obstruction (NO) during growth causes maxillofacial growth suppression, it remains unclear whether eliminating the NO affects maxillary and mandibular growth differentially. We aimed to clarify whether eliminating NO can help regain normal maxillofacial growth and to determine the optimal intervention timing. Forty-two 4-week-old male Wistar rats were randomly divided into six groups. Their left nostril was sutured to simulate NO over different durations in the experimental groups; the sutures were later removed to resume nasal breathing. Maxillofacial morphology was assessed using microcomputed tomography. Immunohistochemical changes in hypoxia-inducible factor (HIF)-1α, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) of the condylar cartilage were evaluated to reveal the underlying mechanisms of these changes. Maxillary length was significantly lower in rats with NO for ≥5 weeks. In groups with NO for ≥7 weeks, the posterior mandibular length, ramus height, thickness of the hypertrophic cell layer in the condylar cartilage, HIF-1α levels, and RANKL levels were significantly lower and OPG levels and RANKL/OPG were significantly higher than those in the control group. Our findings suggest that eliminating NO is effective in regaining maxillofacial growth. Moreover, the optimal timing of intervention differed between the maxilla and mandible.

OPG/RANK/RANKL Axis in Egyptian Children With Acute Lymphoblastic Leukemia After Maintenance Therapy: Relationship to Bone Mineral and Vitamin D Status.

Policies to maximize peak bone mass in survivor's children of acute lymphoblastic leukemia (ALL) have been recognized as a priority area for research. The present study aimed to evaluate the relationship between osteoprotegerin (OPG)/receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) axis, vitamin D status, and serum magnesium in ALL survivors. Sixty ALL survivors treated with chemotherapy and 60 age and sex-matched controls were included. Vitamin D and parathyroid hormone, RANK, RANKL, and OPG levels were immunoassayed, in addition to serum calcium, phosphorus, magnesium levels, and alkaline phosphatase activity assessment. Furthermore, standard anthropometric measurement, history of fractures since treatment and clinical assessment were recorded. History of bone fractures after the start of therapy was detected in 17 ALL subjects (28.33%). Significantly lower vitamin D, magnesium, calcium, and OPG levels, meanwhile, significantly higher serum parathyroid hormone, RANK, and RANKL levels were detected in survivors compared with the control group. Vitamin D level was significantly positively correlated with magnesium, calcium, and OPG levels. Meanwhile, negatively correlated with RANK and RANKL levels. ALL survivors had a high prevalence of impaired vitamin D status, decreased Mg, and altered OPG/RANK/RANKL axis with impaired bone remodeling. The results herein may open the door for new interventional actions in ALL survivors to protect against bone resorption.

Ameliorative Effect of Dabigatran on CFA-Induced Rheumatoid Arthritis via Modulating Kallikrein-Kinin System in Rats.

Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund’s adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat’s hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor–kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis.

Wnt5a-Ror2 signaling mediates root resorption

This study aimed to investigate the role of wingless-type MMTV integration site family member 5a (Wnt5a)-receptor tyrosine kinase-like orphan receptor 2 (Ror2) signaling in root resorption. The messenger RNA (mRNA) expression of Wnt5a, Ror2, and RANKL in periodontal ligament cells (PDLCs) under compression force (CF) with or without Ror2 small interfering RNA (siRNA) were measured by quantitative reverse transcription-polymerase chain reaction, and these proteins released into culture supernatants were measured using enzyme-linked immunosorbent assay. Then these PDLC-conditioned media under CF with or without Ror2 siRNA were used to culture osteoclast precursors to detect osteoclastogenesis effects via tartrate-resistant acid phosphatase staining. In invivo studies, the odontoclast number and the root resorption volume under excessive CF with or without Ror2 siRNA were investigated by tartrate-resistant acid phosphatase immunohistochemical staining and microcomputed tomography. The protein levels for Wnt5a, Ror2, and receptor activator of nuclear factor-kappa B ligand (RANKL) in the periodontal ligament tissues were also detected using immunohistochemical staining. Finally, the odontoclast number, root resorption volume, and the mRNA and protein expressions were compared between immature and mature teeth. The mRNA production and protein release level of Wnt5a, Ror2, and RANKL increased after CF, whereas they were significantly downregulated with Ror2 siRNA. The osteoclast number increased treating with culture medium from PDLC applying CF, but the increase was inhibited after adding Ror2 siRNA. In the animal model, the odontoclast number and root resorption volume significantly increased in the CF group but decreased in the CF with the Ror2 siRNA group. The protein levels of Wnt5a, Ror2, and RANKL in periodontal ligament were upregulated under excessive CF, and the pathway was inhibited with Ror2 siRNA. In the immature tooth group, the odontoclast number, root resorption volume, and the mRNA and protein expressions of Wnt5a-Ror2 signaling were reduced. Wnt5a-Ror2 signaling in PDLCs enhanced by excessive CF could promote RANKL release and induce precursor differentiation, partly leading to increased odontoclast activity and ultimate root resorption. The less resorption of the immature tooth may be due to odontoclastogenesis inhibition by decreased expression of Wnt5a-Ror2 signaling.

Analysis of Biomarkers and Marginal Bone Loss in Platform-Switched and Nonplatform-Switched Implants: A Randomized Clinical Trial.

Objectives To compare the peri-implant crevicular fluid (PICF) biomarker levels, peri-implant status, and marginal bone level (MBL) differences of implants restored with randomly assigned nonplatform-switched (NPS) or platform-switched (PS) abutments. Methods Ninety-four implants in 27 subjects were included in this study. Receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) levels in PICF, peri-implant health, and the change in the MBL were evaluated at the time of restoration (T1) and after 12 months (T2). Results The IL-1β levels decreased and the RANKL, OPG, and MCP-1 levels increased from T1 to T2 (P < 0.05) in both groups. RANKL/OPG ratio at T1, MCP-1 levels at T2, and the MCP-1 change from T1 to T2 were lower in the PS group than in the NPS group (P < 0.05). MBL change was lower (0.51 ± 0.31 mm) in the PS group than that (0.75 ± 0.29 mm) in the NPS group at T2 (P < 0.001). Peri-implant health status between the study groups was negligible. Conclusion PS was superior to NPS regarding the preservation of MBL. Higher MCP-1 levels, altered RANKL/OPG ratio, and lower OPG levels in the NPS group could be associated with subclinical peri-implant bone remodeling.

Evaluation of the Effects of Favipiravir Combined with Vitamin C on Alveolar Bone in Rats.

Introduction: Favipiravir and Vitamin C (Vit C) were used together in the treatment of the COVID-19 pandemic. However, the effects of favipiravir on the periodontium are still unknown. Therefore, the aim of this study was to investigate the effects of Favipiravir and Vit C treatment on alveolar bone metabolism. Experimental: Fifty healthy adult male Sprague-Dawley rats (2–3 months old) were randomly divided into five equal groups (n = 10): Control, Favi 20, Favi 100, Favi 20+Vit C, Favi 100+Vit C. Favipiravir (20 mg/kg and 100 mg/kg, i.m.) and Vit C (150 mg/kg/day, oral) were administered to the rats for 14 days. Alveolar bone loss (ABL) and histopathological changes were examined using a light microscope. Immunohistochemistry was used to determine levels of receptor activator of nuclear factor kappa-B ligand (RANKL), caspase-3, bone morphogenic protein 2 (BMP-2) and alkaline phosphatase (ALP) in the bone tissues. Results: Favipiravir increased the levels of RANKL and caspase-3 expression but decreased BMP-2 and ALP levels in a dose-dependent manner. Favi 20+Vit C and Favi 100 +Vit C groups showed decreased RANKL and caspase-3 levels in addition to increased BMP-2 and ALP levels. Conclusion: Favipiravir can cause histopathological damage to the periodontium, but administration of favipiravir combined with Vit C can provide a protective effect against this damage.

Evaluation of relationship between biochemical parameters and osteoporosis in patients with β-thalassemia major

Background: Osteoporosis is one of the late complications of β-Thalassemia major. The pathogenesis of osteoporosis depends on different factors. Ineffectiveness of hematopoiesis is the major factor, and the other factors are defected by hormonal functions or biochemical parameters. Osteoclasts hyperactivity in thalassemia increases the serum receptor activator of nuclear factor Kappa B ligand (RANKL), which plays a crucial role in bone development. This study aimed to evaluate the biochemical and hormonal parameters in patients with β-thalassemia major and their association with osteoporosis.&#x0D; Materials and Methods: In this case-control study, 52 patients with β-thalassemia major and 23 with thalassemia minor as controls were enrolled. The patients’ Bone Mineral Density (BMD) was measured using the Dual Energy X-ray absorptiometry (DEXA) method, and 6 mL peripheral blood of the patients and controls was obtained to detect hormonal and biochemical parameters. Data were analyzed using ANOVA, Spearman correlation coefficient, and T-test.&#x0D; Results: The mean of BMD in patients was 0.59±0.01 and 0.69±0.11 in femur and vertebrae, respectively. The biochemical parameters in the (patients/ controls) including calcium and alkaline phosphatase (ALK) were 9.1/ 10.2 mg/dL and 171.1/310 IU, respectively indicating a significant decrease (P&lt; 0.05) compared to the controls. On the contrary, the mean levels of Ferritin and Zinc were 1914.18 µg/L and 113.92 mg/mL, respectively which were significantly increased (P= 0.015 and P=0.045, respectively). There was a negative correlation between the femurs BMD of patients with the RANKL level (r= - 0.8, p = 0.034) and the vertebrae BMD of patients with a Parathormone (PTH) level (r= - 0.8, P = 0.028). &#x0D; Conclusion: The study results indicated that the hyperactivity of RANKL and PTH in thalassemia patients might cause osteoporosis; therefore, detecting biomarkers mentioned above could be useful to diagnose osteoporosis.