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Xin Zhang

Xin Zhang

Assistant Professor in Orthopaedic Surgery
Orthopaedic Surgery

Selected Publications

Plasma extracellular vesicles carry immune system-related peptides that predict human longevity.

Journal Article Geroscience · April 2025 Extracellular vesicles (EVs) play crucial roles in aging. In this National Institutes on Aging-funded study, we sought to identify circulating extracellular vesicle (EV) biomarkers indicative of longevity. The plasma EV proteome of 48 older adults (mean ag ... Full text Link to item Cite

Immune System-Related Plasma Pathogenic Extracellular Vesicle Subpopulations Predict Osteoarthritis Progression.

Journal Article Int J Mol Sci · November 21, 2024 Certain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) prog ... Full text Link to item Cite

Immune system-related plasma extracellular vesicles in healthy aging.

Journal Article Front Immunol · 2024 OBJECTIVES: To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults. METHODS: EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial fre ... Full text Link to item Cite

Comprehensive characterization of pathogenic synovial fluid extracellular vesicles from knee osteoarthritis.

Journal Article Clin Immunol · December 2023 Synovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of these EVs are largely unknown. We found that SF EVs contained 692 peptides that were pos ... Full text Link to item Cite

Synergistic roles of CBX4 chromo and SIM domains in regulating senescence of primary human osteoarthritic chondrocytes.

Journal Article Arthritis Res Ther · October 12, 2023 BACKGROUND: Cellular senescence is a critical factor contributing to osteoarthritis (OA). Overexpression of chromobox homolog 4 (CBX4) in a mouse system was demonstrated to alleviate post-traumatic osteoarthritis (PTOA) by reducing cellular senescence. Add ... Full text Open Access Link to item Cite

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Journal Article Arthritis Rheumatol · September 2023 Full text Link to item Cite

Association of Dipeptidylpeptidase 4 (CD26) With Chondrocyte Senescence and Radiographic Progression in Knee Osteoarthritis.

Journal Article Arthritis Rheumatol · July 2023 OBJECTIVE: To evaluate the association of dipeptidylpeptidase 4 (DPP-4; also known as CD26) with cellular senescence of human cartilage and progression of knee osteoarthritis (OA). METHODS: Articular cartilage sections and chondrocytes were acquired from 3 ... Full text Link to item Cite

IL-11 induces NLRP3 inflammasome activation in monocytes and inflammatory cell migration to the central nervous system.

Journal Article Proc Natl Acad Sci U S A · June 27, 2023 The objective of this study is to examine IL-11-induced mechanisms of inflammatory cell migration to the central nervous system (CNS). We report that IL-11 is produced at highest frequency by myeloid cells among the peripheral blood mononuclear cell (PBMC) ... Full text Link to item Cite

Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults.

Journal Article EBioMedicine · November 2022 BACKGROUND: The hard endpoint of death is one of the most significant outcomes in both clinical practice and research settings. Our goal was to discover direct causes of longevity from medically accessible data. METHODS: Using a framework that combines loc ... Full text Link to item Cite

Rejuvenation of neutrophils and their extracellular vesicles is associated with enhanced aged fracture healing.

Journal Article Aging Cell · July 2022 Tissue repair is negatively affected by advanced age. Recent evidence indicates that hematopoietic cell-derived extracellular vesicles (EVs) are modulators of regenerative capacity. Here, we report that plasma EVs carrying specific surface markers indicate ... Full text Link to item Cite

Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells.

Journal Article J Immunol · July 1, 2022 The objective of this study is to determine the mechanism of action of anti-CD52 mAb treatment in patients with relapsing-remitting multiple sclerosis (RRMS). Experimental autoimmune encephalomyelitis (EAE), an animal model of the disease, was used to addr ... Full text Link to item Cite

DPP4 - A POTENTIAL SENESCENT CHONDROCYTE BIOMARKER IN OSTEOARTHRITIS

Journal Article Osteoarthritis and Cartilage · April 2022 Full text Cite

CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.

Journal Article Oxid Med Cell Longev · 2022 Cellular senescence is characterized by cell cycle arrest and senescence-associated secretory phenotypes. Cellular senescence can be caused by various stress stimuli such as DNA damage, oxidative stress, and telomere attrition and is related to several chr ... Full text Link to item Cite

Differential microRNA profiles of intramuscular and secreted extracellular vesicles in human tissue-engineered muscle.

Journal Article Front Physiol · 2022 Exercise affects the expression of microRNAs (miR/s) and muscle-derived extracellular vesicles (EVs). To evaluate sarcoplasmic and secreted miR expression in human skeletal muscle in response to exercise-mimetic contractile activity, we utilized a three-di ... Full text Open Access Link to item Cite

Extracellular Vesicles as Biological Indicators and Potential Sources of Autologous Therapeutics in Osteoarthritis.

Journal Article Int J Mol Sci · August 3, 2021 Along with cytokines, extracellular vesicles (EVs) released by immune cells in the joint contribute to osteoarthritis (OA) pathogenesis. By high-resolution flow cytometry, we characterized 18 surface markers and 4 proinflammatory cytokines carried by EVs o ... Full text Link to item Cite

Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression.

Journal Article Arthritis Rheumatol · January 2021 OBJECTIVE: To evaluate the role of immune cells and their effector cytokines in the pathogenesis and progression of knee osteoarthritis (OA) in matched OA synovial fluid (SF) and synovial tissue samples. METHODS: Cells from matched samples of synovial tiss ... Full text Link to item Cite

TNF-α Carried by Plasma Extracellular Vesicles Predicts Knee Osteoarthritis Progression.

Journal Article Frontiers in immunology · January 2021 ObjectivesTo identify plasma extracellular vesicles (EVs) associated with radiographic knee osteoarthritis (OA) progression.MethodsEVs of small (SEV), medium (MEV) and large (LEV) sizes from plasma of OA participants (n=30) and healthy co ... Full text Cite

Immune cell extracellular vesicles and their mitochondrial content decline with ageing.

Journal Article Immun Ageing · 2020 BACKGROUND: Although the mechanisms of action are not fully understood, extracellular vesicles (EVs) have emerged as key indicators and effectors of immune function. Characterizing circulating EVs associated with stem and immune cells across the lifespan o ... Full text Link to item Cite

IL-11 Induces Encephalitogenic Th17 Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

Journal Article J Immunol · September 1, 2019 IL-11+CD4+ cells accumulate in the cerebrospinal fluid of patients with early relapsing-remitting multiple sclerosis (MS) and in active brain MS lesions. Mouse studies have confirmed a causal role of IL-11 in the exacerbation of relapsing-remitting experim ... Full text Link to item Cite

IL-11 antagonist suppresses Th17 cell-mediated neuroinflammation and demyelination in a mouse model of relapsing-remitting multiple sclerosis.

Journal Article Clin Immunol · December 2018 IL-11 induced differentiation and expansion of Th17 cells in patients with early relapsing-remitting multiple sclerosis (RRMS). In mice with relapsing-remitting experimental autoimmune encephalomyelitis (RREAE), IL-11 exacerbated disease, induced demyelina ... Full text Link to item Cite

Toll-like receptor (TLR)7 and TLR9 agonists enhance interferon (IFN) beta-1a's immunoregulatory effects on B cells in patients with relapsing-remitting multiple sclerosis (RRMS).

Journal Article J Neuroimmunol · September 15, 2016 We report that B cells from patients with RRMS have decreased endogenous IFN-β secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in comparison to healthy controls (HCs), which may contribute to disregulation of cytokine secretion by ... Full text Link to item Cite

Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS.

Journal Article Neurol Neuroimmunol Neuroinflamm · December 2015 OBJECTIVES: To assess potential roles of effector cells and immunologic markers in demyelinating CNS lesion formation, and their modulation by interferon β-1a (IFN-β-1a). METHODS: Twenty-three patients with relapsing-remitting multiple sclerosis (RRMS) rec ... Full text Link to item Cite

Immunological and short-term brain volume changes in relapsing forms of multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: an open-label two-arm trial.

Journal Article BMC Neurol · November 11, 2015 BACKGROUND: Brain volume atrophy is observed in relapsing-remitting multiple sclerosis (RRMS). METHODS: Brain volume changes were evaluated in 23 patients with RRMS treated with interferon β-1a 44 μg given subcutaneously (SC) three times a week (tiw) and 1 ... Full text Link to item Cite

IL-11 in multiple sclerosis.

Journal Article Oncotarget · October 20, 2015 Full text Link to item Cite

IL-11 Induces Th17 Cell Responses in Patients with Early Relapsing-Remitting Multiple Sclerosis.

Journal Article J Immunol · June 1, 2015 Clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) is the earliest clinically evident phase of the disease, which may provide valuable insight into the molecular mechanisms of the initiation of the autoimmune response in MS. Our resul ... Full text Link to item Cite

The role of fractalkine (CX3CL1) in regulation of CD4(+) cell migration to the central nervous system in patients with relapsing-remitting multiple sclerosis.

Journal Article Clin Immunol · April 2015 Fractalkine (CX3CL1) levels are increased in the cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS), as well as in the CSF and serum samples from patients with relapsing-remitting multiple sclerosis (RRMS). A higher percentage of ... Full text Link to item Cite

The role of endogenous IFN-β in the regulation of Th17 responses in patients with relapsing-remitting multiple sclerosis.

Journal Article J Immunol · June 15, 2014 IFN-β has been used as a first-line therapy for relapsing-remitting multiple sclerosis (RRMS). Because only a few studies have addressed the role of endogenous IFN-β in the pathogenesis of the disease, our objective was to characterize its role in the tran ... Full text Link to item Cite

Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis.

Journal Article J Immunol · December 15, 2013 Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to characterize the immunological reconstitution of T cell subsets and its contribution to the ... Full text Link to item Cite

Simvastatin inhibits secretion of Th17-polarizing cytokines and antigen presentation by DCs in patients with relapsing remitting multiple sclerosis.

Journal Article Eur J Immunol · January 2013 Statins, widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects. Here, we characterize the capacity of simvastatin to target DCs and modulate T-cell priming and Th17-cell differentiation, in a cohort of patien ... Full text Link to item Cite

CX(3)CR1 drives cytotoxic CD4(+)CD28(-) T cells into the brain of multiple sclerosis patients.

Journal Article J Autoimmun · February 2012 Immunosenescence, or ageing of the immune system, contributes to the increased morbidity and mortality seen in the elderly population. Premature immunosenescence is shown to occur in a subgroup of patients with autoimmune diseases. One of the main characte ... Full text Link to item Cite

Simvastatin inhibits IFN regulatory factor 4 expression and Th17 cell differentiation in CD4+ T cells derived from patients with multiple sclerosis.

Journal Article J Immunol · September 15, 2011 Subsequent to the clinical trial of simvastatin in patients with relapsing remitting multiple sclerosis (RR MS), which demonstrated the ability of simvastatin to inhibit new inflammatory CNS lesion formation, the current in vitro study has characterized th ... Full text Link to item Cite

Interferon beta inhibits the Th17 cell-mediated autoimmune response in patients with relapsing-remitting multiple sclerosis.

Journal Article Clin Neurol Neurosurg · September 2010 Interferon (IFN)beta has been used over the past decades as an effective first-line therapy against relapsing-remitting multiple sclerosis (RR MS), however its in vivo operative mechanisms of action are not fully understood. Current advances in our underst ... Full text Link to item Cite

IFN-beta inhibits human Th17 cell differentiation.

Journal Article J Immunol · October 15, 2009 IFN-beta-1a has been used over the past 15 years as a primary therapy for relapsing-remitting multiple sclerosis (MS). However, the immunomodulatory mechanisms that provide a therapeutic effect against this CNS inflammatory disease are not yet completely e ... Full text Link to item Cite

IFN-beta1a inhibits the secretion of Th17-polarizing cytokines in human dendritic cells via TLR7 up-regulation.

Journal Article J Immunol · March 15, 2009 IFN-beta, an effective therapy against relapsing-remitting multiple sclerosis, is naturally secreted during the innate immune response against viral pathogens. The objective of this study was to characterize the immunomodulatory mechanisms of IFN-beta targ ... Full text Link to item Cite

Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells.

Journal Article Clin Immunol · February 2009 In this study, acute and chronic brain and spinal cord lesions, and normal appearing white matter (NAWM), were resected post-mortem from a patient with aggressive relapsing-remitting multiple sclerosis (MS). T-cell infiltrates from the central nervous syst ... Full text Link to item Cite

Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes.

Journal Article J Immunol · May 15, 2008 Statins, extensively used as cholesterol-lowering agents, have recently been identified as immunomodulatory agents. This study investigated the statins' mechanisms that target the autoimmune response in humans, and evaluated their therapeutic potential in ... Full text Link to item Cite

Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: implications for the initiation of the autoimmune response in multiple sclerosis.

Journal Article Eur J Immunol · May 2008 TCR degeneracy may facilitate self-reactive T cell activation and the initiation of an autoimmune response in multiple sclerosis (MS). MHC class II alleles of the DR2 haplotype DR2a (DRB5*0101) and DR2b (DRB1*1501) are associated with an increased risk for ... Full text Link to item Cite

Statins' immunomodulatory potential against Th17 cell-mediated autoimmune response.

Journal Article Immunol Res · 2008 Statins' recently discovered anti-inflammatory effects place them at the forefront of the new therapies for chronic inflammatory and autoimmune diseases. Our recent study demonstrated that simvastatin exerts an independent immunomodulatory effect on the hu ... Full text Link to item Cite