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ID PMID Title PublicationDate abstract
15621381 Parent-child interactions among children with juvenile fibromyalgia, arthritis, and health 2005 Jan Parent-child interactions during pain-inducing exercise tasks among children (11-17 years old) with fibromyalgia, juvenile rheumatoid arthritis, and pain-free controls were examined and the contribution of parent-child interactions to disability was tested. Fifteen children in each of the three diagnostic groups and their parents completed 5-min exercise tasks and completed questionnaire measures of disability (Functional Disability Inventory) and coping (Pain Coping Questionnaire). There were few group differences in parent-child interactions. After controlling for children's ratings of pain evoked by the exercise, group differences in interactions during exercise tasks were no longer significant. Sequential analyses, controlling for group and exercise task, revealed that when parents made statements discouraging coping following children's negative verbalizations about the task or pain, children were less likely to be on task, compared to when parents made statements encouraging coping or when parents made any other statements. Children's general pain coping strategies were not related to parent-child interactions. Parent-child interactions were generally not related to disability. Across the groups, more pain and less time on task during the exercises were related to Functional Disability Inventory scores and more school absences. Parent-child interaction patterns influence children's adaptation to pain during experimental tasks. Parents' discouragement of coping in response to their children's negative statements related to the pain or the pain-evoking task are counter productive to children's ability to maintain activity in a mildly painful situation.
16622521 Microarray analyses of peripheral blood cells identifies unique gene expression signature 2005 Jan Psoriatic arthritis (PsA) is a chronic and erosive form of arthritis of unknown cause. We aimed to characterize the PsA phenotype using gene expression profiling and comparing it with healthy control subjects and patients rheumatoid arthritis (RA). Peripheral blood cells (PBCs) of 19 patients with active PsA and 19 age- and sex-matched control subjects were used in the analyses of PsA, with blood samples collected in PaxGene tubes. A significant alteration in the pattern of expression of 313 genes was noted in the PBCs of PsA patients on Affymetrix U133A arrays: 257 genes were expressed at reduced levels in PsA, and 56 genes were expressed at increased levels, compared with controls. Downregulated genes tended to cluster to certain chromosomal regions, including those containing the psoriasis susceptibility loci PSORS1 and PSORS2. Among the genes with the most significantly reduced expression were those involved in downregulation or suppression of innate and acquired immune responses, such as SIGIRR, STAT3, SHP1, IKBKB, IL-11RA, and TCF7, suggesting inappropriate control that favors proin-flammatory responses. Several members of the MAPK signaling pathway and tumor suppressor genes showed reduced expression. Three proinflammatory genes--S100A8, S100A12, and thioredoxin--showed increased expression. Logistic regression and recursive partitioning analysis determined that one gene, nucleoporin 62 kDa, could correctly classify all controls and 94.7% of the PsA patients. Using a dataset of 48 RA samples for comparison, the combination of two genes, MAP3K3 followed by CACNA1S, was enough to correctly classify all RA and PsA patients. Thus, PBC gene expression profiling identified a gene expression signature that differentiated PsA from RA, and PsA from controls. Several novel genes were differentially expressed in PsA and may prove to be diagnostic biomarkers or serve as new targets for the development of therapies.
16313350 Immune responses and bone loss: the estrogen connection. 2005 Dec In addition to its effects on sexual differentiation and reproduction, estrogen has important impact on the immune system and on bone. It has also been evident that the effects of estrogen on bone to a large extent are mediated via its action on immune cells. Estrogen has a dichotomous impact on the immune system by downregulation of inflammatory immune responses but simultaneous upregulation of immunoglobulin production. Consequently, immune-mediated diseases in humans and in animal models are modulated by estrogen. Estrogen deficiency after ovariectomy in mice and after menopause in women is associated with significant bone loss. In rheumatic diseases such as rheumatoid arthritis (RA), osteoporosis is frequent, and in patients with postmenopausal RA, the degree of bone loss is dramatically increased. Hormone replacement therapy (HRT) in murine and human arthritis has beneficial effects on bone loss, as expected, but it also ameliorates inflammation and inflammation-triggered joint destruction. Long-term use of HRT has been associated with increased risk of breast cancer, thrombosis, and possibly also stroke. Accordingly, there is great need for new activators of estrogen receptors (ERs) selectively reproducing only the beneficial effects of estrogen. To achieve this aim, better knowledge of the mechanisms of how activation of ER-alpha and ER-beta modulates the immune system and bone at the cellular and molecular levels is necessary.
17097618 Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in 2007 Jan 1 Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) has been reported to be therapeutically efficacious in the treatment of rheumatoid arthritis (RA), but its in vivo actions have not been clarified. The purpose of this study was to investigate the effects of triptolide, a diterpenoid triepoxide extracted from TWHF, on inflammation and cartilage destruction in collagen-induced arthritis (CIA) model mice. Histological examination demonstrated that triptolide significantly reduced the inflammatory responses and cartilage damage in the joint tissues. Interestingly, triptolide interfered with CIA-augmented expression of matrix metalloproteinases-13 and -3, which are considered to be key enzymes in the pathological destruction of cartilage, and simultaneously augmented CIA-reduced tissue inhibitors of metalloproteinases-1 and -2 expression in the joints. Moreover, triptolide inhibited prostaglandin E(2) production via selective suppression of the production and gene expression of cyclooxygenase (COX)-2, but not COX-1. The levels of interleukin (IL)-1beta, tumor necrosis factor alpha and IL-6 were also decreased by triptolide in the joint tissues and sera as well as the suppression of CIA-mediated expression of their mRNAs in the joints. In addition, triptolide treatment in vivo was able to reduce an abundance of nuclear factor-kappaB, the transcriptional factor closely related to the inflammatory process, in articular cartilage and synovium in CIA mice. These results suggest that triptolide exerts novel chondroprotective and anti-inflammatory effects on RA, and the therapeutic action of TWHF on RA is, in part, due to the triptolide activities.
15934096 Angiotensin receptor blockers suppress antigen-specific T cell responses and ameliorate co 2005 Jun OBJECTIVE: The renin-angiotensin system plays an important role in the regulation of cardiovascular, renal, and endocrine functions. Recent studies have demonstrated that angiotensin II has proinflammatory effects that may contribute to the pathogenesis of immune-mediated diseases. We used the collagen-induced arthritis (CIA) model to investigate the influence of angiotensin II receptor blockers (ARBs) on antigen-specific immune responses and determine whether ARBs have preventive or therapeutic effects on the development of arthritis. METHODS: We administered ARBs (olmesartan, candesartan, and telmisartan) to mice and evaluated antigen-specific T cell proliferation and cytokine production following immunization with ovalbumin (OVA) or type II collagen in Freund's complete adjuvant (CFA) or aluminum hydroxide (alum). Next, we induced CIA in DBA/1 mice and administered olmesartan. The severity and incidence of arthritis were scored according to clinical manifestations, and joint tissue sections were examined histopathologically. RESULTS: ARBs severely suppressed lymphocyte proliferation and interferon-gamma production in mice immunized with OVA or type II collagen in CFA. Olmesartan also suppressed lymphocyte proliferation in mice immunized with ovalbumin in alum. In the CIA model, olmesartan reduced the mean arthritis score and the incidence of severe arthritis, even when it was administered only after disease onset. Histopathologic findings for joint destruction were improved in olmesartan-treated mice. CONCLUSION: ARBs suppressed antigen-specific immune responses for Th1 and Th2 in vivo. Furthermore, olmesartan suppressed the development of severe arthritis and joint destruction in the CIA model. These findings suggest that ARBs may have therapeutic potential in rheumatoid arthritis.
15681827 Circulating CD26 is negatively associated with inflammation in human and experimental arth 2005 Feb Dipeptidyl peptidase IV (DPPIV, CD26), a protease-cleaving N-terminal X-Pro dipeptide from selected proteins including some chemokines, is expressed both as a soluble form in plasma and on the cell surface of various immune and nonimmune cell types. To gain insights into the pathophysiological role of CD26 in arthritis, we explored DPPIV/CD26 expression during murine antigen-induced arthritis (AIA), an experimental model of arthritis. AIA induction led to reduced plasma DPPIV activity. In CD26-deficient mice, the severity of AIA was increased as assessed by enhanced technetium uptake and by increased histological parameters of inflammation (synovial thickness and exudate). We demonstrated that CD26 controls the in vivo half-life of the intact active form of the proinflammatory chemokine stromal cell-derived factor-1 (SDF-1). CD26-deficient mice exhibited increased levels of circulating active SDF-1, associated with increased numbers of SDF-1 receptor (CXCR4)-positive cells infiltrating arthritic joints. In a clinical study, plasma levels of DPPIV/CD26 from rheumatoid arthritis patients were significantly decreased when compared to those from osteoarthritis patients and inversely correlate with C-reactive protein levels. In conclusion, decreased circulating CD26 levels in arthritis may influence CD26-mediated regulation of the chemotactic SDF-1/CXCR4 axis.
15688190 Evidence-based use of methotrexate in children with rheumatic diseases: a consensus statem 2005 Apr Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with non-steroidal anti-inflammatory drugs (NSAID) and physiotherapy. However, in a significant number of cases the disease is resistant to this therapy, and treatment with "second line" disease-modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as "first-choice second-line agent" for the treatment of JIA. To increase drug safety, the Working Groups for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words "Methotrexate" and "juvenile arthritis" limited to age 0-18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin DRFZ), experience with MTX in adults with rheumatoid arthritis (RA), and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded, and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.
16633930 Expansion of large granular lymphocytes following Pseudomonas infection in a patient with 2006 We report a patient who had a 4-year history of adult-onset Still's disease (AOSD) and showed a prominent increase in large granular lymphocytes (LGL) when she developed severe Pseudomonas conjunctivitis due to Pseudomonas aeruginosa, skin eruptions, liver damage, and abnormal findings in coagulation studies, without any evidence of active viral activation, hemophagocytosis, or malignancies. The increased LGL cells were CD3(+)CD8(+), and disappeared promptly after the administration of antibiotics combined with prednisolone, with subsequent stabilization of her general condition.
16567554 Dental plaque pH and micro-organisms during hyposalivation. 2006 Apr We have previously reported that minor gland and whole saliva flow rates and salivary proteins showed differences in individuals with primary Sjögren's syndrome or head and neck radiation therapy, compared with controls (Eliasson et al., 2005). We now hypothesize that pH and number of acidogenic micro-organisms in dental plaque as well as saliva buffering capacity also differ in these individuals. Plaque pH was measured by the microtouch method up to 60 min after a sucrose rinse. Plaque collected from the same sites was analyzed for counts of total and acidic micro-organisms. Compared with their controls, the irradiated group but not the Sjögren's syndrome group displayed significantly lower plaque pH, increased numbers of lactobacilli and Candida species, as well as reduced buffering capacity. Stepwise regression tests suggested that the buccal minor-salivary-gland secretion rate in the test groups and counts of mutans streptococci in the controls were of significant importance for dental plaque pH.
16889286 Ibuprofen-induced fever in Sjogren's syndrome. 2006 A 68-year-old woman with a medical history significant for Sjögren syndrome and leukocytoclastic vasculitis of small vessels presented to the emergency department with chills, malaise, a temperature of 39 degrees C, nausea, vomiting, and hypotension. Fifteen minutes earlier she had taken ibuprofen for flu-like symptoms. She was treated with a perfusion of intravenous saline, paracetamol, and ciprofloxacin with improvement 24 hours later. Three months later, she had a similar episode, without hypotension. An oral challenge test with ibuprofen in the hospital produced the same symptoms 3 hours after the last dose. She was treated with metamizole and paracetamol and was asymptomatic the next day. This is the first report of a febrile reaction to ibuprofen in a patient with Sjogren's syndrome.
16273862 [Lymphoproliferative disorders in Sjögren's syndrome]. 2005 INTRODUCTION: Sjögren's syndrome [SS] is an autoimmune disease that mainly affects the exocrine glands. B-cell lymphoproliferation is a characteristic feature of this syndrome and the lesion may range from benign to malignant. MATERIAL AND METHODS: After a systematic search of Pubmed we reviewed literature regarding the histopathology, pathophysiology and clinics of lymphoproliferation in SS. RESULTS: Patients with Sjögren's syndrome [SS] have over 40-fold increased risk of the development B-cell non-Hodgkin's lymphoma. Most cases of lymphomas complicating the course of SS arise in mucosal extranodal sites, especially in the salivary gland, and are classified as low grade marginal zone B-cell lymphoma with long-term survival. The main problem in salivary lymphoproliferation in Sjögren's syndrome consists in the difficulties in the differential diagnosis of lymphoma. Genotypic studies have documented the rearrangement of immunoglobulin genes across the full spectrum of lymphoid infiltrates in the salivary gland including cases regarded as reactive lymphoepithelial sialadenitis [LESA], borderline cases with halos of monocytoid cells surrounding epimyoepithelial islets, and cases with fully developed marginal zone lymphoma [MZL]. Thus, the simple detection of B-cell clonality cannot be used as a criterion for the diagnosis of B-cell malignancy. Broad strands of monocytoid B-cells that surround and invade epimyoepithelial islets and monotypic immunoglobulin expression detected by immunohistochemistry are an essential feature for the histopathological diagnosis of MZL. The pathophysiology of lymphoma in SS remains still unknown. Viral infection, hyperstimulation of B cells, disregulation in the process of apoptosis, and unknown oncogenes are suspected to initiate the start of lymphoma. The main clinical features associated with the development of lymphoma in SS include persistent major salivary gland enlargement (> 2 months), persistent lymphadenopathy or splenomegaly, monoclonal gammapathy and type II mixed cryoglobulinemia. The treatment and prognosis of lymphoma associated with SS depend on the type and stage of lymphoma. CONCLUSION: Patients with SS develop a variety B lymphoproliferative disorders. The nature of these must be determined by multiparameter analysis including clinical, histopathological, immunohistochemical and genotypic studies.
15965638 Endothelial dysfunction in patients with primary Sjögren's syndrome. 2005 Sep The aim of this study was to determine the endothelial function in patients with primary Sjögren's syndrome (SS). We also aimed to determine whether endothelial (dys)function correlates with extraglandular manifestations, specific autoantibodies and the severity of salivary gland involvement of SS. Endothelium-dependent vasodilation and endothelium-independent vasodilation of the brachial artery were assessed by a high-resolution ultrasound on 25 patients with primary SS and on 29 healthy controls. Patients with primary SS had significantly less mean endothelium-dependent vasodilation than did controls (3.0 +/- 0.4% vs 4.2 +/- 0.3%; p = 0.012). Endothelium-independent vasodilation induced by sublingual glycerol trinitrate was not different between the two groups (12.9 +/- 1.4% vs 14.1 +/- 1.2%; p = 0.86). We concluded that endothelium-dependent vasodilation was impaired in primary SS patients, in particular those presenting with Raynaud's phenomenon, when compared with the healthy controls and this impairment was not associated with the presence of RF, ANA, anti-Ro/SS-A, anti-La/SS-B and with the other extraglandular manifestations of the disease.
16305638 The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on Sjögren' 2005 Nov Systemic autoimmune diseases, such as Sjögren's syndrome (SS), are characterized by a complex aetiology with multiple pathogenic factors. In SS, disturbed B-cell biology and humoral immunity including B-cell-activating factor (BAFF)-mediated processes have been described. Dysregulated BAFF expression has been described to lead to disease progression and perpetuation of humoral autoimmunity. Moreover, BAFF has been proposed to contribute to the development of B-cell malignancies. In this review, we summarize the current knowledge on BAFF with regard to SS pathology and discuss special features such as germinal centre (GC) formation and lymphomagenesis. Locally, in SS salivary glands, the reduced level of apoptosis among BAFF-expressing cells might lead to longer-existing BAFF expression and thereby maintain signalling for tissue-infiltrating B cells to proliferate and supposedly to become autoantibody-producing plasma cells. We assume that prolonged BAFF signalization may contribute to GC formation and/or lymphoma development in the disease. Finally, we discuss possibilities of novel treatments targeting the BAFF-system in SS.
15952907 Gene therapeutics in Sjögren's syndrome. 2005 Jun Sjögren's syndrome (SS) is a complex autoimmune disorder, characterised by mononuclear cell infiltration of exocrine glands, principally the lacrimal and salivary glands. Both cellular, in the form of autoreactive immune cells, and humoral factors, such as autoantibodies, contribute to the expression of the disease. SS can also occur as a systemic disease affecting several organs, and approximately 5% of the patients develop malignant lymphoproliferation. Today SS is considered uncurable. The treatment available is only palliative, and the treatment goals are to manage symptoms and prevent or limit tissue damage. This may involve both local and systemic measures. However, the existing systemic treatment of chronic inflammatory autoimmune diseases has several limitations and unwanted side effects. In recent years the possibility to treat diseases with gene therapy has gained interest and has become a subject of investigation. Given the multitude of factors contributing to the pathogenesis of SS, gene therapy is a major challenge, but may elicit great benefits if successful. Keeping this in mind, the possibility for gene therapeutics in SS in general and potential targets for gene therapy are discussed.
15730179 Sjögren's syndrome diagnosed in pregnancy: a case report. 2005 Jan BACKGROUND: As in most other autoimmune diseases, Sjögren's syndrome is seen predominantly in women. Since the peak age is around the late reproductive and early postmenopausal period, the obstetric aspect has not been well studied. CASE: A 28-years-old woman, pregnant for 22 weeks and 5 days, was admitted with worsening general status, skin lesions, arthralgias, and oral and ocular symptoms typical of Sjögren's syndrome. She underwent hemodialysis for renal insufficiency. To prevent autoantibody formation, progression of the disease, therapy with methyl prednisolone, 100 mg/d intravenously; cyclophosphamide, 500 mg/month in a single intravenous application; hemodialysis 3 times a week; and plasmapheresis 7 times was instituted. An 1,100-g, male infant at 27 weeks and 5 days was delivered by cesarean section because of premature preterm rupture of membranes and severe late decelerations on cardiotocography. The infant was discharged from the neonatal intensive care unit after 30 days, weighing 1,800 g. Postnatal echocardiographic examination of the infant revealed neither cardiac malformations nor arrhythmias. CONCLUSION: Since the presence of autoantibodies against SS-A and SS-B are reported to accompany congenital heart block, the primary goal of therapy should be preventing this untoward effect of the disease. Close monitoring during pregnancy is mandatory to detect preeclampsia, intrauterine growth retardation and preterm labor.
15899047 CD134 as target for specific drug delivery to auto-aggressive CD4+ T cells in adjuvant art 2005 T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60, indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system. Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis. Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate disease development.
16520943 CC chemokine receptor (CCR)-2 prevents arthritis development following infection by Mycoba 2006 Jun The host factors that influence autoimmune arthritides such as rheumatoid arthritis have not been fully elucidated. We previously found that genetic inactivation of CC chemokine receptor 2 (CCR2) in the arthritis-prone DBA/1j mouse strain significantly increases the susceptibility of this strain to autoimmune arthritis induced by immunization with collagen type II (CII) and complete Freund's adjuvant (CFA). Here, we show that following intradermal infection with Mycobacterium avium, a similar arthritis phenotype was detected in Ccr2-null mice in the DBA/1j, but not in the BALB/c background. The failure to develop arthritis in Ccr2-null BALB/c mice occurred in the face of high bacterial burdens and low interferon gamma (IFNgamma) production. By contrast, Ccr2-null DBA/1j mice had low bacterial burdens, produced normal amounts of IFNgamma, and had high titers of autoantibodies against CII. Thus, the Ccr2-null state in an arthritic-prone genetic background leads to increased arthritis susceptibility following infectious (M. avium) and noninfectious (CII/CFA) challenges. Because CCR2 serves as a negative regulator of murine arthritis, caution might need to be exercised while testing CCR2 blockers in human arthritis or other diseases. These findings also indicate that Ccr2-null DBA/1j mice might serve as a valuable model system to uncover the immunological determinants of arthritis and to test novel antiarthritic agents.
16704745 Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer 2006 IL-10 is a Th2 cytokine important for inhibiting cell-mediated immunity while promoting humoral responses. Human IL-10 (hIL-10) has anti-inflammatory, immunosuppressive as well as immunostimulatory characteristics, whereas viral IL-10 (vIL-10), a homologue of hIL-10 encoded by Epstein Barr virus (EBV), lacks several immunostimulatory functions. The immunostimulatory characteristic of hIL-10 has been attributed to a single amino acid, isoleucine at position 87, which in vIL-10 is alanine. A mutant hIL-10 in which isoleucine has been substituted (mut.hIL-10) is biologically active with only immunosuppressive, but not immunostimulatory, functions, making it a potentially superior therapeutic for inflammatory diseases. To compare the efficacy of mut.hIL-10 with hIL-10 and vIL-10 in blocking the progression of rheumatoid arthritis, we used replication defective adenoviral vectors to deliver intra-articularly the gene encoding hIL-10, vIL-10 or mut.hIL-10 to antigen-induced arthritic (AIA) knee joints in rabbits. Intra-articular expression of hIL-10, vIL-10, and mut.hIL-10 resulted in significant improvement of the pathology in the treated joints to similar levels. These observed changes included a significant reduction in intra-articular leukocytosis and the degree of synovitis, as well as normalization of cartilage matrix metabolism. Our results suggest that hIL-10, vIL-10, and mut.hIL-10 are all equally therapeutic in the rabbit AIA model for treating disease pathology.
17349384 [Elbow arthroscopy: intra-articular pathologies.]. 2006 Nov Elbow arthroscopy has become to be the most useful tool for the treatment of many intra-articular affections of the elbow. Radiological statement is necessary including plain radiographs and CT or MR arthrography before performing arthroscopy. Loose bodies are the more frequent indication, they are often related with an other intra-articular pathology. The others indications for an elbow arthroscopy can be, osteochondritis dissecans, synovial fringe, synovitis especially rheumatoid arthritis and arthritic elbow. The treatment of this different pathologies is discribe keeping in mind the potential risks especially neurological.
16164211 [The regulation of osteoclastogenesis by IFN]. 2005 Sep Bone homeostasis is maintained by the balanced activities of two bone specific cell types: bone-resorbing osteoclasts and bone-forming osteoblasts. Since the disorder of osteoclast differentiation and/or activity leads to bone diseases such as postmenopausal osteoporosis, rheumatoid arthritis, etc., it is central to identify factors that regulate osteoclastogenesis and to study the regulatory mechanisms. Here, we show IFNs (IFN-beta and IFN-gamma) as new regulators of osteoclastogenesis: each IFN inhibits osteoclastogenesis via different molecular mechanisms. We also show the regulation of osteoblastogenesis by Stat1, an essential transcription factor for IFN signal. Our research will shed light on the novel cross-talk between IFN signals and bone cells (Table 1).