IRF7 overexpression alleviates CFA-induced inflammatory pain by inhibiting nuclear factor-κB activation and pro-inflammatory cytokines expression in rats.

BACKGROUND: It is known that nerve signals arising from sites of inflammation lead to persistent changes in the spinal cord and contribute to the amplification and persistence of pain. Nevertheless, the underlying mechanisms have not yet been completely elucidated. We identified differentially expressed genes in the lumbar (L4-L6) segment of the spinal cord from complete Freund's adjuvant (CFA) rats compared to control animals via high throughput sequencing. Based on differential gene expression analysis, we selected interferon regulatory factor 7 (IRF7) for follow-up experiments to explore its antinociceptive potential. METHODS: An animal model of inflammatory pain was induced by intraplantar injection of CFA. We evaluated the effects of adeno-associated viral (AAV)-mediated overexpression of IRF7 in the spinal cord on pain-related behavior after CFA injection. Moreover, the activation of the nuclear factor-κB (NF-κB) and the expression of inflammatory cytokines were investigated to understand the underlying mechanisms related to the contribution of IRF7 to inflammatory pain. RESULTS: CFA intraplantar injection caused a significant decrease in the level of spinal IRF7, which is mainly expressed in the dorsal horn neurons and astrocytes. Moreover, IRF7 overexpression significantly attenuated pain-related behaviors, as well as the activity of NF-κB/p65 and the production of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the spinal cord of CFA rats. CONCLUSIONS: Our data indicated that spinal IRF7 plays an important role in the regulation of inflammatory pain. Thus, IRF7 overexpression at the spinal cord level might represent a potential target for the treatment of inflammatory pain.

ASSESSING THE ACTIVITY OF MYOPIC CHOROIDAL NEOVASCULARIZATION: Comparison Between Optical Coherence Tomography Angiography and Dye Angiography.

PURPOSE: This study aims to suggest a novel strategy for assessing the activity of myopic choroidal neovascularization (mCNV) based on optical coherence tomography angiography (OCTA) and to compare it with traditional fundus fluorescein angiography as the gold standard. METHODS: Macular OCTA images were obtained using RTVue XR Avanti with AngioVue. Morphologic features of mCNV lesions were analyzed. Characteristics of OCTA in 41 eyes with active mCNV and 41 eyes with inactive mCNV were analyzed. Optical coherence tomography angiography parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using fundus fluorescein angiography as the reference. RESULTS: Of the total 108 patients, 82 had OCTA images with good quality which were included in this study. Several anatomical features of the CNV lesions, including overall appearance, branching with tiny vessels, presence of anastomoses/loops, and choroidal dark halo, were considered the possible parameters associated with mCNV activity. The intra- and interobserver agreements were substantial. To evaluate the CNV activity, sensitivity of overall appearance, tiny vascular branching, and presence of anastomoses or loops were 65.9%, 82.9%, and 73.2%, respectively, whereas the specificity was 87.8%, 90.2%, and 92.7%, respectively. However, the choroidal dark halo showed low specificity (46.3%) and failed in terms of evaluating the activity of mCNV. A novel comprehensive procedure integrating branching as a major parameter and overall appearance and presence of anastomoses/loops as minor parameters was developed to evaluate mCNV activity with sensitivity of 95.1% and specificity of 85.4%. CONCLUSION: In mCNV, the acquisition rate of clear OCTA images was 75.9%. A novel comprehensive diagnostic procedure combining mCNV appearance, vascular branching, and anastomoses/loops by OCTA may be a valuable strategy to evaluate neovascular activity in mCNV.

IL-33/ST2 signaling contributes to radicular pain by modulating MAPK and NF-κB activation and inflammatory mediator expression in the spinal cord in rat models of noncompressive lumber disk herniation.

BACKGROUND: Immune and inflammatory responses occurring in the spinal cord play a pivotal role in the progression of radicular pain caused by intervertebral disk herniation. Interleukin-33 (IL-33) orchestrates inflammatory responses in a wide range of inflammatory and autoimmune disorders of the nervous system. Thus, the purpose of this study is to investigate the expression of IL-33 and its receptor ST2 in the dorsal spinal cord and to elucidate whether the inhibition of spinal IL-33 expression significantly attenuates pain-related behaviors in rat models of noncompressive lumbar disc herniation. METHODS: Lentiviral vectors encoding short hairpin RNAs that target IL-33 (LV-shIL-33) were constructed for gene silencing. Rat models of noncompressive lumber disk herniation were established, and the spines of rats were injected with LV-shIL-33 (5 or 10 µl) on the first day after the operation. Mechanical thresholds were evaluated during an observation period of 21 days. Moreover, the expression levels of spinal tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclooxygenase 2 (COX-2) and the activation of the mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) pathways were evaluated to gain insight into the mechanisms related to the contribution of IL-33/ST2 signaling to radicular pain. RESULTS: The application of nucleus pulposus (NP) to the dorsal root ganglion (DRG) induced an increase in IL-33 and ST2 expression in the spinal cord, mainly in the dorsal horn neurons, astrocytes, and oligodendrocytes. Spinally delivered LV-shIL-33 knocked down the expression of IL-33 and markedly attenuated mechanical allodynia. In addition, spinal administration of LV-shIL-33 reduced the overexpression of spinal IL-1ß, TNF-α, and COX-2 and attenuated the activation of C-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and NF-κB/p65 but not p38. CONCLUSIONS: This study indicates that spinal IL-33/ST2 signaling plays an important role in the development and progression of radicular pain in rat models of noncompressive lumber disk herniation. Thus, the inhibition of spinal IL-33 expression may provide a potential treatment to manage radicular pain caused by intervertebral disk herniation.

Enhanced TLR5-dependent migration and activation of antigen-loaded airway dendritic cells by flagellin.

TLR5 agonist flagellin is an effective mucosal adjuvant via intranasal administration. Previous studies demonstrated that the mucosal adjuvanticity of flagellin depends on TLR5 signaling of airway epithelial cells. Since dendritic cells play a central role in antigen sensitization and the initiation of primary immune responses, we wondered how dendritic cells were modulated by the intranasally administrated flagellin. In this study, a mouse model of intranasal immunization with ovalbumin, a model antigen, in the presence or absence of flagellin was utilized. We found that nasal administration of flagellin enhanced the coadministered antigen-specific antibody responses and T-cell clonal expansion in a TLR5-dependent manner. However, neither the entering of flagellin to nasal lamina propria nor the uptake of coadministered antigen by nasal resident dendritic cells was associated with TLR5 signaling. In contrast, migration of antigen-loaded dendritic cells from the nasal cavity to the cervical lymph nodes and activation of dendritic cells in the cervical lymph nodes were both enhanced through TLR5 signaling. Furthermore, for the dendritic cells, flagellin enhanced the expression of CCR7, which was pivotal for dendritic cells in the priming site migrating to draining lymph nodes. Interestingly, the migration, activation, and chemokine receptor expression levels of antigen-loaded dendritic cells were all significantly higher than that of bystander dendritic cells. In conclusion, intranasally administrated flagellin enhanced TLR5-dependent antigen-loaded dendritic cells' migration and activation but not antigen uptake.

Inhibition of Spinal Interleukin-33 Attenuates Peripheral Inflammation and Hyperalgesia in Experimental Arthritis.

Accumulating evidence indicates that the continuous and intense nociceptive from inflamed tissue may increase the excitability of spinal dorsal horn neurons, which can signal back and modulate peripheral inflammation. Previous studies have demonstrated that spinal interleukin (IL)-33 contributes to the hyperexcitability of spinal dorsal horn neurons. This study was undertaken to investigate whether spinal IL-33 can also influence a peripheral inflammatory response in a rat model of arthritis. Lentivirus-delivered short hairpin RNA targeting IL-33 (LV-shIL-33) was constructed for gene silencing. Rats with adjuvant-induced arthritis (AIA) were injected intrathecally with LV-shIL-33 3 days before the complete Freund's adjuvant (CFA) injection. During an observation period of 21 days, pain-related behavior and inflammation were assessed. In addition, the expression of spinal proinflammatory cytokines and the activation of spinal extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB) pathways were evaluated on 9 days after CFA treatment. The existence of tissue injury or inflammation in rats with AIA resulted in the upregulation of spinal IL-33, which is predominantly expressed in neurons, astrocytes, and oligodendrocytes. Intrathecal administration of LV-shIL-33 significantly alleviated hyperalgesia, paw swelling, and joint destruction, and attenuated the expression of proinflammatory cytokines [IL-6, IL-1ß, and tumor necrosis factor-α (TNF-α)], as well as the activation of ERK and NF-κB/p65 in the spinal cord. Our data suggest that spinal IL-33 contributes to the development of both peripheral inflammation and hyperalgesia. Thus, interference with IL-33 at the spinal level might represent a novel therapeutic target for painful inflammatory disorders.

Interleukin-33 modulates lipopolysaccharide-mediated inflammatory response in rat primary astrocytes.

Astrocytes have a crucial role in the modulation of the neuroinflammatory response. However, the underlying mechanisms have yet to be fully defined. Interleukin-33 (IL-33) is constitutively expressed in astrocytes, which has been found to orchestrate inflammatory responses in a large variety of immune-mediated and inflammatory diseases of the nervous system. Thus, the purpose of this study was to elucidate the potential effect of IL-33 in the regulation of inflammatory response in primary cultured astrocytes. We investigated the role of IL-33 in the regulation of inflammatory responses in the lipopolysaccharide-stimulated astrocytes. This study utilized lentiviral short hairpin RNA vectors to target IL-33 (LV-shIL-33) for gene silencing. After lipopolysaccharide stimulation, the expression levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α), as well as the activation of nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) signaling pathways, were evaluated to elucidate the mechanisms related to the contributions of IL-33 to the inflammatory response in astrocytes. We found that the expression IL-33 has increased in rat primary cultured astrocytes after lipopolysaccharide stimulation. Administration of LV-shIL-33 knocked down the expression of IL-33 and markedly reduced the overexpression of spinal IL-1ß, IL-6, and TNF-α, and attenuated the activation of ERK and NF-κB/p65. This study shows that IL-33 participates in regulating inflammatory responses in primary cultured astrocytes, which might provide additional targets for controlling inflammatory responses following neurological diseases. See Video abstract, http://links.lww.com/WNR/A627.

Clinical features of ocular toxocariasis: a comparison between ultra-wide-field and conventional camera imaging.

PURPOSE: The purpose of this study is to compare the lesion detection rates of ocular toxocariasis (OT) between ultra-wide-field scanning laser ophthalmoscopy (UWF-SLO) and conventional fundus photography (CFP), and to evaluate the potential diagnostic ability of UWF-SLO in OT. METHODS: A total of 56 patients with serological/immunological confirmed unilateral OT were enrolled. The presence of OT characteristic features included the posterior granuloma (postG), peripheral granuloma (periG), tractional retinal detachment (TRD), retinal folds (RF), and vitreous strands (VS) and was analyzed in 36 patients with UWF-SLO and 56 patients with CFP. Diagnostic tests were employed using the clinical examination as gold standard. RESULTS: In total of the 56 OT eyes, granulomas were identified in 91.1% (51/56) of eyes, including postG in 46.4% (26/56) of eyes, periG in 41.1% (23/56) of eyes, and combined granulomas in 3.6% (2/56) of eyes. TRD, RF, and VS were found in 28.6% (16/56), 51.8% (29/56), and 83.9% (47/56) of patients, respectively. Although the specificities of the diagnosis in clinical features were similar by the diagnostic tests, the sensitivities of postG, periG, TRD, RF, and VS using UWF-SLO were 100%, 100%, 66.7%, 95%, and 81.8%, respectively, which were significantly higher those of CFP (72.2%, 31.3%, 11.1%, 55%, and 48.5%). Additionally, the extent of vitreous haze was milder graded by UWF-SLO compared to CFP (p = 0.0099). CONCLUSIONS: The diagnostic ability of UWF-SLO was superior to CFP using clinical examination as gold standard for the ascertainment of the characteristic manifestations of OT, especially for granulomas and RF.

Parental genetic knowledge and attitudes toward childhood genetic testing for inherited eye diseases.

BACKGROUND: This study aimed to explore the parental genetic knowledge and attitudes toward childhood genetic testing of the inherited eye diseases (IEDs) in China. METHODS: This is a cross-sectional survey. All parents were assessed via self-administered questionnaires. Data were collected through the Internet at the pediatric eye clinics in a tertiary referral eye hospital. RESULTS: In total, 359 parents were included into this survey. The proportion of correctly answered the factual genetic knowledge questionnaire ranged from 35.7% to 81.3%, which is positively correlated to the educational levels and household per capita income. The attitudes toward childhood IEDs genetic testing appeared to be consistent. More factual genetic knowledge was predictive for a favorable attitude toward genetic testing. Han Chinese might be slightly more likely to have a favorable attitude. Interestingly, the higher educational levels and lower monthly incomes were predictive factors for a reserved attitude toward genetic testing. The families without history of IEDs were more inclined to remain a reserved attitude than those with family history of IEDs. CONCLUSION: This study illustrated that more factual genetic knowledge was considered as an indicator for the favorable attitudes. Therefore, the effective strategies should be taken to provide the correct knowledge of genetics and genetic testing to parents, especially those who need to make an informed decision thereon to undertake childhood genetic testing.

Analysis of Etiologic Factors in Pediatric Rhegmatogenous Retinal Detachment With Genetic Testing.

PURPOSE: The purpose of this study was to investigate the etiology and clinical features of nontraumatic rhegmatogenous retinal detachment (RRD) in children. DESIGN: Consecutive, cross-sectional study. METHODS: In this study, 112 operative eyes of 102 patients ≤18 years of age with nontraumatic RRD were included. Comprehensive ophthalmic examinations were performed in all patients. Genetic testing was performed in 34 patients with hereditary congenital/developmental diseases. The etiology of RRD was analyzed. RESULTS: The average age was 12.2 ± 4.5 years (range, 1-18 years). The percentages of male and female patients were 74.5% (76/102) and 25.5% (26/102), respectively. The most common etiologic factors were congenital/developmental anomalies (51/102, 50%), followed by simple myopia (34/102, 33.3%) and previous intraocular surgery (6/102, 5.9%). More than half (31/51, 60.8%) of the patients with congenital/developmental anomalies had familial exudative vitreoretinopathy. Further analysis of the underlying etiologic factors based on age revealed that the most common etiology of RRD in patients ≤12 years of age was congenital/developmental anomalies (28/48, 58.3%); however, simple myopia was the major etiologic factor in patients >12 years of age (27/54, 50%). CONCLUSIONS: Congenital/developmental diseases were the most common etiologies of pediatric nontraumatic RRD in China. Familial exudative vitreoretinopathy accounted for most of the congenital/developmental anomalies.

Identification of Novel Copy Number Variations of VCAN Gene in Three Chinese Families with Wagner Disease.

The VCAN/versican gene encodes an important component of the extracellular matrix, the chondroitin sulfate proteoglycan 2 (CSPG2/versican). Heterozygous variants targeting exon 8 of VCAN have been shown to cause Wagner disease, a rare autosomal dominant non-syndromic vitreoretinopathy that induces retinal detachment, cataracts and permanent visual loss. In this study, we report on six patients from three unrelated families with Wagner disease in whom we identified three novel copy number variations of VCAN. Quantitative real-time polymerase chain reaction analysis identified deletions, including one exon-intron boundary of exon 8 or both exons 8 and 9, causing the haploinsufficiency of VCAN mRNAs.

Developmental Changes in Retinal Microvasculature in Children: A Quantitative Analysis Using Optical Coherence Tomography Angiography.

PURPOSE: To quantify the macular microvasculature in healthy children of various ages by using optical coherence tomography angiography (OCTA). DESIGN: Prospective cross-sectional study. METHODS: A total of 333 normal children from 4 to 16 years old were included. OCTA was performed on a 3- × 3-mm area centered on the macular region. Vascular density, perfusion density, fovea avascular zone (FAZ) area, FAZ perimeter, and FAZ acircularity index (AI) were measured and adjusted for axial length. Differences were compared among various ages. RESULTS: Among the different age groups, both macular vascular density and perfusion density increased with age (P < .0001 and P = .0028, respectively). After adjustments were made for the spherical equivalent (SE) and axial length, macular vascular density was significantly associated with age (r = 0.183; P = .001) No factors were significantly correlated with the perfusion density after adjustment for the age, SE, or axial length. The FAZ area and FAZ perimeter did not change among groups of different ages. Nevertheless, the AI of FAZ in the 4.00-6.99-year-old group was smaller to that of the 13.00-15.99-year-old group (P = .03). Younger children had significantly higher rates of nonconsecutive vessels branched toward the macular center (P = .0002) and vascular loops contributing to irregular shapes of FAZ (P = .024). CONCLUSIONS: Macular vascular density and perfusion density continuously increase with age in children. Despite the fact that FAZ area and perimeter did not change, the microstructure of FAZ pruned and tended to form a smooth and regular avascular area during development.

Next-Generation Sequencing in the Familial Exudative Vitreoretinopathy-Associated Rhegmatogenous Retinal Detachment.

Purpose: The purpose of this study was to investigate the genetic mutation spectrum in Chinese patients with familial exudative vitreoretinopathy-associated rhegmatogenous retinal detachment (FEVR-RRD) and to analyze the preliminary genotype-phenotype association. Methods: In this consecutive, cross-sectional study, 54 patients with FEVR-RRD were studied. Comprehensive ophthalmic examinations and targeted next-generation sequencing were performed in all patients. The genotype-phenotype association was also analyzed. Results: Causative mutations were identified in 38.9% (21/54) of patients (14/54 in LRP5, 4/54 in FDZ4, and 3/54 in TSPAN12). The study identified 22 potentially pathogenic mutations in 21 unrelated FEVR probands, and 14 were novel (10/15 in LRP5, 1/4 in FZD4, and 3/3 in TSPAN12). Furthermore, to explore the genotype-phenotype association, late-phase angiographic posterior and peripheral leakage (LAPPEL) was identified in 100% (4/4) of patients with FZD4 mutations and 100% (3/3) of patients with TSPAN12 mutations but only in 42.9% (6/14) of patients with LRP5 mutations. Extraretinal neovascularization (ERNV) was found in 100% (4/4) of patients with FZD4 mutations and in 66.7% (2/3) of patients with TSPAN12 mutations, but only in 21.4% (3/14) of patients with LRP5 mutations. Conclusions: The positive rate for pathogenic mutations in the known FEVR-associated genes was 38.9% (21/54). Among the mutations, LRP5 mutation was the predominant, accounting for 66.7% (14/21) of genetic positive patients. Patients with FEVR-RRD due to LRP5 mutations have less retinal vascular leakage or neovasculization than do patients with FEVR-RRD due to TSPAN12/FZD4 mutations. Moreover, 14 novel variants were found, which provided a deeper understanding of this disease.

Parents' perceptions of diagnostic genetic testing for children with inherited retinal disease in China.

BACKGROUND: In this study, we aim to investigate the awareness of, attitudes toward, and experiences with diagnostic genetic testing among parents of children suspected of having inherited retinal disease (IRDs) in China. METHODS: Semistructured, face-to-face, and in-depth interviews were carried out with parents of children with suspected IRDs in this qualitative study. Inductive content analysis was used for data processing. RESULTS: Forty-six parents participated in our interviews, and 47.8% of them supported genetic testing for following four main reasons: to help in making informed reproductive health decisions, to prepare for novel potential treatment, to identify the underlying causes of IRDs, and to satisfy curiosity about the heredity of IRDs. Among them, 19.6% were opposed to the testing for four main reasons, namely lack of therapeutic benefit, difficulty in affording the testing cost, doubt in the accuracy of clinical diagnosis, and the presence of concerns about the limitations of genetic testing. 47.8% of the parents expressed concerns that the genetic findings might lead to potential psychological stress. CONCLUSION: In this study, we showed that nearly half of the parents supported genetic testing mainly for family planning, and a fifth of the parents were opposed to the testing mainly for lack of therapeutic benefit. Moreover, half of the parents expressed concern that a positive genetic result may create potential psychological burden to the parents and children.

Prevalence and Determinants Associated With Spectacle-Wear Compliance in Aphakic Infants.

PURPOSE: We assess the prevalence of spectacle wear and the factors associated with compliance among aphakic infants with congenital cataracts who underwent lens extraction in South China. METHODS: Infants aged 3 months to 3 years were enrolled from among participants in the Childhood Cataract Program of the Chinese Ministry of Health (CCPMOH). The prevalence and potential determinants of spectacle-wearing compliance were identified from interviews with the infants' caregivers. RESULTS: Among 192 infant caregivers, the mean (SD) age of the infants was 1.89 (0.50) years, and 57% were males. Compliance was 30.9% in the 3-month- to 1-year-old age group, 78.0% in the 1- to 2-year-old age group, and 87.0% in the 2- to 3-year-old age group. The following two factors were associated with spectacle-wearing compliance: softness of the spectacles frame (ß = 1.273, P = 0.002, odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.6-8.0) and communication with other caregivers regarding the spectacle-wearing experience (ß = -2.955, P = 0.034, OR = 0.1, 95% CI = 0-0.8). CONCLUSIONS: Compliance with spectacle wear was low during the earlier stage, but increased with time in aphakic infants. However, overall compliance should be improved. Therefore, efficient strategies aimed at improving spectacle-wearing compliance are needed. TRANSLATIONAL RELEVANCE: These findings reveal the low spectacle-wearing compliance in aphakic infants and support useful information to improve compliance.

Inhibition of periostin gene expression via RNA interference suppressed the proliferation, apoptosis and invasion in U2OS cells.

BACKGROUND: Periostin originally designated osteoblast-specific factor 2 (OSF-2) is frequently found to be highly expressed in various types of human cancer cell lines in vitro and human cancer tissues in vivo. We proposed that periostin was a key factor during the process of proliferation and invasion in cancer cells. We investigated the effect of periostin on the function of human osteosarcoma cell line (U2OS), such as proliferation, apoptosis, invasion and the associated signal pathway. METHODS: A human PGCsi/U6 promoter-driven DNA template was adopted to induce short hairpin RNA (shRNA)-triggered RNA interference (RNAi) to block periostin gene expression in the cell line U2OS. U2OS cells were divided into three groups: cells transfected with phosphate buffered saline as control group (the U2OS group), cells transfected with pGCsi as negative control group (the NC group) and cells transfected with periostin/pGCsi as experimental group (the pGCsi-periostin group). Then, transfection efficiency of cell was observed under fluorescent microscope. The expressions of periostin and the related genes in cells were detected by reverse transcription polymerase chain reaction and Western Blotting. Cell viability was determined using the methyl-thiazolyl tetrazolium bromide (MTT) quantitative colorimetric assay. The invasion and migration capability of cells were tested by transwell plates with or without extracellular matrix gel. Furthermore, the changes of cell cycle and apoptosis were analyzed by flow cytometry. RESULTS: The transfection efficiency of periostin/pGCsi to U2OS cells was about 70% - 80%. When compared with the NC group, the levels of mRNA and protein of periostin in the pGCsi-periostin group decreased by 82% (F = 564.71, P < 0.001) and 58% (F = 341.51, P < 0.001), respectively. Meantime, the earlier apoptosis value increased by 417% (F = 28.69, P < 0.001). The percentage of S phase pGCsi-periostin cells decreased by 21% (F = 47.00, P < 0.001), however, that of G0 - G1 phase cells increased by 12% (F = 14.50, P < 0.001). The capability of migration and invasion reduced by 41% (F = 17.79, P < 0.001) and 72% (F = 197.08, P < 0.001), respectively. The cell proliferation in the pGCsi-periostin group decreased by 59% and 72% at 48 and 120 hours after transfection, respectively. The mRNA expressions of transforming growth factor-ß and vascular endothelial growth factor decreased by 17% (F = 73.99, P < 0.001) and 47% (F = 30.25, P < 0.001), respectively. A tendency of lower focal adhesion kinase (FAK) was shown in pGCsi-periostin cells but without any statistically significant difference. Otherwise the expression of p-FAK in those cells had markedly decreased by 21% (F = 16.81, P < 0.001). CONCLUSIONS: RNAi against periostin can effectively down-regulate periostin gene expression. Periostin increases the hyperplasia and invasion of cancer cells. Periostin might be involved in and served as a tumor promoter gene in the pathogenesis of osteosarcoma.