Mature dendritic cells (DC) are efficient, antigen-presenting cells required for the stimulation of naive T lymphocytes. Many members of the tumour necrosis factor (TNF) receptor family are involved in DC maturation, such as Fas, CD40, OX40L, LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) or RANK (receptor activator of NFkappaB), with different, but often overlapping effects. We focused our attention on RANK DC stimulation, since RANK ligand (RL) is expressed on activated T lymphocytes with different kinetic and expression patterns from the other members of TNF family previously cited. After culture with RL-transfected cells, a significant percentage of immature DC generated from monocytes (Mo-DC) acquired a typical, mature DC morphology and phenotype characterised by up-regulation of CD83, DC-LAMP (lysosome-associated membrane glycoprotein), HLA class I, CD86 and CD54. The functional RL-mediated maturation was demonstrated by a decrease in DC macropinocytosis and acquisition of the capacity to stimulate allogenic T-cells. Among the various cytokines tested, we detected only a weak up-regulation of IL-12p40. Our results show that ligation of RANK on DC cell surfaces is not only a survival stimulus, but also induces a partial and specific mature DC phenotype, the physiological significance of which is under investigation.
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http://dx.doi.org/10.1684/ecn.2008.0125 | DOI Listing |
Objective: Aim: To evaluate the role of maxillary bone inflammation in the formation of MSCs through the comprehensive assessment of histological and radiological research results and the determination of receptor activator of nuclear factor kappa-B (RANKL) in tissue homogenates, nasal secretions, and blood plasma.
Patients And Methods: Materials and Methods: We included 25 patients aged 20 to 65 with maxillary sinus cysts. We analyzed computed tomography and used enzyme-linked immunosorbent assay with human TNFSF11 (RANKL) in biological samples.
JCI Insight
December 2024
Infection Biology Program, Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Patients with immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) are at higher risk for severe COVID-19 and long-term complications in bone health. Emerging clinical evidence demonstrated that SARS-CoV-2 infection reduces bone turnover and promotes bone loss, but the mechanism underlying worsened bone health remains elusive. This study sought to identify specific immune mediators that exacerbated preexisting IMIDs after SARS-CoV-2 exposure.
View Article and Find Full Text PDFBMC Musculoskelet Disord
December 2024
Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Institute of Science Tokyo), 1-5-45 Yushima Bunkyo-Ku, Tokyo, 113-8519, Japan.
Background: The rapid decline in ovarian function associated with menopause promotes osteoclast differentiation and increases bone resorption, disrupting of bone homeostasis and increasing the risk of osteoporosis. Hyaluronic acid (HA) is a polysaccharide ubiquitously present in the connective tissues. Recent reports indicate that high-molecular-weight HA (HMW-HA) promotes osteoblast proliferation, enhances alkaline phosphatase activity and mineral deposition, and promotes the expression of bone differentiation markers, such as Runx2 and osteocalcin.
View Article and Find Full Text PDFMol Med
December 2024
Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Background: Bone remodeling is a critical process that maintains skeletal integrity, orchestrated by the balanced activities of osteoclasts, which resorb bone, and osteoblasts, which form bone. Osteoclastogenesis, the formation of osteoclasts, is primarily driven by NFATc1, a process activated through c-Fos and NF-κB signaling pathways in response to receptor activator of nuclear factor κB ligand (RANKL). Dysregulation of RANKL signaling is a key contributor to pathological bone loss, as seen in conditions such as osteoporosis.
View Article and Find Full Text PDFClin Transl Sci
December 2024
Clinical Pharmacology Research Center, Huashan Hospital, Fudan University, Shanghai, China.
Denosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel-group, two-part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants.
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