Chuan-ju Liu

Bio: Chuan-ju Liu is an academic researcher from New York University. The author has contributed to research in topics: Arthritis & Chondrocyte. The author has an hindex of 45, co-authored 162 publications receiving 6409 citations. Previous affiliations of Chuan-ju Liu include Yale University & Veterans Health Administration.

The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice

Abstract: The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFα-TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis.

Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty.

Abstract: Background: The erythrocyte sedimentation rate, the C-reactive protein serum level, and the white blood-cell count are routinely used to diagnose periprosthetic infection. In the present study, the diagnostic accuracy of the interleukin-6 serum level was compared with the accuracy of these standard tests for the evaluation of a group of patients who had had a total hip or total knee arthroplasty and were undergoing a reoperation for the treatment of an infection or another implant-related problem. Methods: A prospective, case-control study of fifty-eight patients who had had a total hip or knee replacement and were undergoing a reoperation because of an infection (seventeen patients) or another implant-related problem (forty-one patients) was conducted. The serum levels of interleukin-6 and C-reactive protein, the erythrocyte sedimentation rate, and the white blood-cell count were measured. The definitive diagnosis of an infection was determined on the basis of positive histopathological evidence of infection and growth of bacteria on culture of intraoperative specimens. Two-sample Wilcoxon rank-sum (Mann-Whitney) tests were used to determine the presence of a significant difference between patients with and without infection with regard to each laboratory value studied. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each text were also calculated. Results: The serum interleukin-6 level, erythrocyte sedimentation rate, and C-reactive protein level were significantly higher in patients who had an infection than in those who did not, both when all patients were considered together and when the total hip arthroplasty and total knee arthroplasty groups were considered separately. With the numbers available, there was no significant difference with regard to the white blood-cell count between patients with and without infection. With a normal serum interleukin-6 level defined as <10 pg/mL, the serum interleukin-6 test had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 1.0, 0.95, 0.89, 1.0, and 97%, respectively. Conclusions: An elevated serum interleukin-6 level correlated positively with the presence of periprosthetic infection in patients undergoing a reoperation at the site of a total hip or knee arthroplasty. The serum interleukin-6 level is valuable for the diagnosis of periprosthetic infection in patients who have had a total hip or total knee arthroplasty. Level of Evidence: Diagnostic Level IV. See Instructions to Authors for a complete description of levels of evidence.

ADAMTS-7 Mediates Vascular Smooth Muscle Cell Migration and Neointima Formation in Balloon-Injured Rat Arteries

Abstract: The migration of vascular smooth muscle cells (VSMCs) plays an essential role during the development of atherosclerosis and restenosis. Extensive studies have implicated the importance of extracellular matrix (ECM)-degrading proteinases in VSMC migration. A recently described family of proteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), is capable of degrading vascular ECM proteins. Here, we sought to determine whether ADAMTS-7 is involved in VSMC migration and neointima formation in response to vascular injury. ADAMTS-7 protein accumulated preferentially in neointima of the carotid artery wall after balloon injury. In primary VSMCs, ADAMTS-7 level was enhanced by the proinflammatory cytokine tumor necrosis factor α and growth factor platelet-derived growth factor-BB. ADAMTS-7 overexpression greatly accelerated and small interfering RNA knockdown markedly retarded VSMC migration/invasion in vitro. In addition, luminal delivery of ADAMTS-7 adenovirus to carotid arteries exacerbated intimal thickening nearly sixfold 7 days after injury. Conversely, perivascular administration of ADAMTS-7 small interfering RNA but not scramble small interfering RNA to injured arteries attenuated intimal thickening by 50% at 14 days after injury. Furthermore, ADAMTS-7 mediated degradation of the vascular ECM cartilage oligomeric matrix protein (COMP) in injured vessels. Replenishing COMP circumvented the promigratory effect of ADAMTS-7 on VSMCs. Enforced expression of COMP significantly suppressed VSMC migration and neointima formation postinjury, which indicates that ADAMTS-7 facilitated intimal hyperplasia through degradation of inhibitory matrix protein COMP. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and postangioplasty restenosis.

Insights into the role of progranulin in immunity, infection, and inflammation

Abstract: PGRN, a pleiotrophic growth factor, is known to play an important role in the maintenance and regulation of the homeostatic dynamics of normal tissue development, proliferation, regeneration, and the host-defense response and therefore, has been widely studied in the fields of infectious diseases, wound healing, tumorigenesis, and neuroproliferative and degenerative diseases. PGRN has also emerged as a multifaceted immune-regulatory molecule through regulating the signaling pathways known to be critical for immunology, especially TNF/TNFR signaling. In this review, we start with updates about the interplays of PGRN with ECM proteins, proteolytic enzymes, inflammatory cytokines, and cell-surface receptors, as well as various pathophysiological processes involved. We then review the data supporting an emerging role of PGRN in the fields of the "Cubic of I", namely, immunity, infection, and inflammation, with special focus on its regulation of autoimmune syndromes. We conclude with insights into the immunomodulating, anti-inflammatory, therapeutic potential of PGRN in treating diseases with an inflammatory etiology in a vast range of medical specialties.

Antiviral Actions of Interferons

Abstract: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.

New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society.

Abstract: Based on the proposed criteria, definite PJI exists when: (1) There is a sinus tract communicating with the prosthesis; or (2) A pathogen is isolated by culture from at least two separate tissue or fluid samples obtained from the affected prosthetic joint; or (3) Four of the following six criteria exist: (a) Elevated serum erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) concentration, (b) Elevated synovial leukocyte count, (c) Elevated synovial neutrophil percentage (PMN%), (d) Presence of purulence in the affected joint, (e) Isolation of a microorganism in one culture of periprosthetic tissue or fluid, or (f) Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at ×400 magnification. PJI may be present if fewer than four of these criteria are met.

The Fibroblast Growth Factor signaling pathway

Abstract: The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs) Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer © 2015 Wiley Periodicals, Inc

IFI16 is an innate immune sensor for intracellular DNA.

Abstract: The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-β (IFN-β). IFI16 directly associated with IFN-β-inducing viral DNA motifs. STING, a critical mediator of IFN-β responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-κB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).