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Background: Condoliase-induced chemonucleolysis is a less-invasive alternative treatment for lumbar disc herniation (LDH); however, its long-term clinical outcome is still unclear. This study aimed to investigate 1-year clinical outcomes and assess radiographs after chemonucleolysis with condoliase.Methods: We enrolled patients with LDH who received condoliase injection with a follow-up period of >1 year. Sixty patients (37 men, 23 women; mean age, 44.5 ± 18.9 years; mean follow-up period, 22.0 ± 6.0 months) were analyzed. Changes in disc height and degeneration were evaluated using magnetic resonance imaging. Visual analog scale (VAS) scores for leg and back pain and the Oswestry disability index (ODI) were obtained. All data were assessed at baseline, 1-month, 3-month, and 1-year follow-up.Results: Surgical treatment was subsequently required in 8 patients (12.5%) after condoliase therapy. Their ODI and VAS scores for leg pain and back pain significantly improved at 1 year, as in those who received condoliase therapy only. On MRI, progression of Pfirrmann grade was observed in 23 patients (44.2%) at 3 months; however, 8 patients recovered to baseline at 1 year. The mean disc height decreased at 3 months; however, it recovered at 1 year. Disc height recovery (disc recovery rate >50%) was observed in 30.8% of the patients. Patients with disc height recovery were significantly younger than those without. Patients with longer symptom duration (≥1 year) showed significantly lower rates of effectiveness compared with those with shorter symptom durations (<1 year).Conclusions: Chemonucleolysis with condoliase is a safe and minimally invasive treatment. Disc degeneration induced by chemonucleolysis could be recovered, particularly in younger patients. Prolonged symptom duration had adverse effects on outcome; thus, therapeutic intervention at the optimal time is needed. [ABSTRACT FROM AUTHOR]

Background: Condoliase is a novel, potent chemonucleolytic drug available for clinical use for lumbar disc herniation (LDH) in Japan. The aim of this study was to assess the clinical outcome of condoliase therapy in patients with LDH, as well as factors affecting the clinical outcome.Methods: We enrolled patients with LDH who were receiving condoliase injection. The following baseline data were collected: symptom duration; herniation level and type; T2 signal intensity of herniation; adverse events; rates of spondylolisthesis, posterior intervertebral angle of ≥5°, and vertebral body translation of ≥3 mm. Change in disc height, disc degeneration, herniation size, visual analog scale (VAS) for leg and back pain, and Oswestry Disability Index (ODI) were evaluated at the baseline, and 3-month follow-up. These data were compared between patients with efficacious (VAS improvement of ≥20 mm; group E) and inefficacious (VAS improvement <20 mm or required operation; group I) for condoliase treatment.Results: Forty-seven patients (20 women, 27 men; mean age 48 years) were included. The herniation level was L2/3 in one patient, L3/4 in two, L4/5 in 23, and L5/S1 in 21. Median symptom duration was 8 months. The mean VAS and ODI improved significantly from the baseline to 3-month follow-up (p < 0.01). Group E included 33 patients (70.2%) and group I included 14, three of whom had a history of discectomy. The rates of spondylolisthesis and posterior intervertebral angle ≥5° were significantly higher in group I than in group E. However, the rates of trans-ligamentous type and herniation with high signal intensity on T2-weighted images (highT2) were significantly higher in group E. Reduction of disc herniation was more frequently observed in group E.Conclusions: Condoliase injection resulted in significantly improved symptoms in patients with LDH. Condoliase therapy was less effective for patients with a history of discectomy, spondylolisthesis, or those with a posterior intervertebral angle ≥5°, while trans-ligamentous type and high T2 herniation were associated with increased efficacy. [ABSTRACT FROM AUTHOR]

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is associated with increasing age, obesity, and diabetes mellitus. However, little is known about the clinical impacts of DISH on physical function and spinal deformity in elderly populations. The purpose of this study was to elucidate the influence of DISH on physical function, spinal deformity, and health-related quality of life (HRQOL) in elderly populations.Methods: We enrolled 504 volunteers (203 men and 301 women, mean age 74.0 years). Height, weight, body mass index (BMI), blood pressure, grip strength, one-leg standing time, sit-and-reach, functional reach, and bone mineral density (BMD) were measured. Using whole spine standing X-rays, the prevalence, location, and numbers of fused vertebra of DISH and spinopelvic parameters were measured. HRQOL measures, including the Oswestry Disability Index and the EuroQuol-5D were also obtained. We compared DISH subjects with control subjects of age and sex matching. We compared DISH subjects in the thoracic spine (T-DISH) to those in the thoraco-lumbar spine (TL-DISH).Results: DISH occurred more frequently in men (14.3%) than in women (4.3%). The mean age was significantly higher of subjects with DISH than of those without DISH. The mean number of fused vertebra by DISH was 5.5 ± 1.5, and T-DISH was observed in 57% cases. DISH group showed greater body weights, BMIs, blood pressures, and BMD in the lumbar spine compared to the control group. No inter-group differences were observed in physical function, HRQOL and spinopelvic parameters. Subjects with TL-DISH had significantly lower values of sit-and-reach and functional reach than those with T-DISH.Conclusions: Subjects with DISH showed greater body weights, BMIs, blood pressures, and BMD compared to age- and sex-matched controls, while physical function, spinal alignment, and HRQOL were comparable between groups. [ABSTRACT FROM AUTHOR]

The incidence of second hip fractures occurring within a year of initial fractures is 20%–45%. The high incidence of second hip fractures in this period can be attributed to the rapid bone loss that occurs during this time. Restoring bone mass at an early stage after hip fractures is critical for preventing subsequent fractures. The aim of this study was to investigate the efficacy of monthly minodronate therapy (50 mg/4 wk) for preventing bone loss over a 9-mo period following hip fractures. Minodronate was administered monthly to 51 patients (44 females), beginning within 3 mo after hip fracture surgery. The mean (±standard deviation) age of the patients was 82.0 ± 0.9 yr. Demographics, mobility status, bone turnover makers, and bone mineral density (BMD) in the lumbar spine and proximal femur (including femoral neck and total hip BMD) were examined prior to and after 9 mo of treatment. Lumbar BMD was increased by 2.7% ± 4.4% ( p  < 0.001) compared to the baseline values. However, femoral neck and total hip BMD did not significantly change. Bone formation and resorption markers both decreased by approximately 70% during treatment. Monthly treatment with minodronate did not adversely affect the healing process on the fracture site or the patients' laboratory results. The patients who were independently mobile prior to injury exhibited greater recovery of BMD in the femoral neck during the 9-mo treatment period. Monthly minodronate therapy during the early stages after hip fractures has favorable effects on restoring overall lumbar BMD and contralateral femoral neck BMD in patients with independent mobility prior to fractures. [ABSTRACT FROM AUTHOR]

In inflamed tissue, normal signal transduction pathways are altered by extracellular signals. For example, the JNK pathway is activated in psoriatic skin, which makes it an attractive target for treatment. To define comprehensively the JNK-regulated genes in human epidermal keratinocytes, we compared the transcriptional profiles of control and JNK inhibitor-treated keratinocytes, using DNA microarrays. We identified the differentially expressed genes 1, 4, 24, and 48 h after the treatment with SP600125. Surprisingly, the inhibition of JNK in keratinocyte cultures in vitro induces virtually all aspects of epidermal differentiation in vivo: transcription of cornification markers, inhibition of motility, withdrawal from the cell cycle, stratification, and even production of cornified envelopes. The inhibition of JNK also induces the production of enzymes of lipid and steroid metabolism, proteins of the diacylglycerol and inositol phosphate pathways, mitochondrial proteins, histones, and DNA repair enzymes, which have not been associated with differentiation previously. Simultaneously, basal cell markers, including integrins, hemidesmosome and extracellular matrix components, are suppressed. Promoter analysis of regulated genes finds that the binding sites for the forkhead family of transcription factors are over-represented in the SP600125-induced genes and c-Fos sites in the suppressed genes. The JNK-induced proliferation appears to be secondary to inhibition of differentiation. The results indicate that the inhibition of JNK in epidermal keratinocytes is sufficient to initiate their differentiation program and suggest that augmenting JNK activity could be used to delay cornification and enhance wound healing, whereas attenuating it could be a differentiation therapy-based approach for treating psoriasis. [ABSTRACT FROM AUTHOR]

Identification of tumor necrosis factor α (TNFα) as the key agent in inflammatory disorders led to new therapies specifically targeting TNFα and avoiding many side effects of earlier anti-inflammatory drugs. However, because of the wide spectrum of systems affected by TNFα, drugs targeting TNFα have a potential risk of delaying wound healing, secondary infections, and cancer. Indeed, increased risks of tuberculosis and carcinogenesis have been reported as side effects after anti-TNFα therapy. TNFα regulates many processes (e.g. immune response, cell cycle, and apoptosis) through several signal transduction pathways that convey the TNFα signals to the nucleus. Hypothesizing that specific TNFα-dependent pathways control specific processes and that inhibition of a specific pathway may yield even more precisely targeted therapies, we used oligonucleotide microarrays and parthenolide, an NF-κB-specific inhibitor, to identify the NF-κB-dependent set of the TNFα-regulated genes in human epidermal keratinocytes. Expression of ∼40% of all TNFα-regulated genes depends on NF-κB; 17% are regulated early (1–4 h post-treatment), and 23% are regulated late (24–48 h). Cytokines and apoptosis-related and cornification proteins belong to the ‘early’ NF-κB-dependent group, And antigen presentation proteins belong to the ‘late’ group, whereas most cell cycle, RNA-processing, and metabolic enzymes are not NF-κB-dependent. Therefore, inflammation, immunomodulation, apoptosis, And differentiation are on the NF.KB pathway, and cell cycle, metabolism, and RNA processing are not. Most early genes contain consensus NF-κB binding sites in their promoter DNA and are, presumably, directly regulated by NF-κB, except, curiously, the cornification markers. Using siRNA silencing, we identified cFLIP/CFLAR as an essential NF-κB-dependent antiapoptotic gene. The results confirm our hypothesis, suggesting that inhibiting a specific TNFα-dependent signaling pathway may inhibit a specific TNFα-regulated process, leaving others unaffected. This could lead to more specific anti-inflammatory agents that are both more effective and safer. [ABSTRACT FROM AUTHOR]

Identification of tumor necrosis factor-α (TNFα) as the key agent in inflammatory disorders, e.g. rheumatoid arthritis, Crohn's disease, and psoriasis, led to TNFα-targeting therapies, which, although avoiding many of the sideeffects of previous drugs, nonetheless causes other side-effects, including secondary infections and cancer. By controlling gene expression, TNFα orchestrates the cutaneous responses to environmental damage and inflammation. To define TNFα action in epidermis, we compared the transcriptional profiles of normal human keratinocytes untreated and treated with TNFα for 1, 4, 24, and 48 h by using oligonucleotide microarrays. We found that TNFα regulates not only immune and inflammatory responses but also tissue remodeling, cell motility, cell cycie, and apoptosis. Specifically, TNFα regulates innate immunity and inflammation by inducing a characteristic large set of chemokines, including newly identified TNFα targets, that attract neutrophils, macrophages, and skinspecific memory T-cells. This implicates TNFα in the pathogenesis of psoriasis, fixed drug eruption, atopic and allergic contact dermatitis. TNFα promotes tissue repair by inducing basement membrane components and collagen-degrading proteases. Unexpectedly, TNFα induces actin cytoskeleton regulators and integrins, enhancing keratinocyte motility and attachment, effects not previously associated with TNFα. Also unanticipated was the influence of TNFα upon keratinocyte cell fate by regulating cell-cycle and apoptosis-associated genes. Therefore, TNFα initiates not only the initiation of inflammation and responses to injury, but also the subsequent epidermal repair. The results provide new insights into the harmful and beneficial TNFα effects and define the mechanisms and genes that achieve these outcomes, both of which are important for TNFα-targeted therapies. [ABSTRACT FROM AUTHOR]

This study aimed to clarify sex differences in the relationship between trunk muscle mass, aging, and whole-body sagittal alignment. Subjects aged 60–89 years who underwent musculoskeletal screening in 2018 were included in the study. Subject demographics, trunk muscle mass (TMM) measured by bioelectrical impedance analysis (BIA), and spinopelvic and lower extremity alignment parameters measured from standing radiographic images were investigated. Additionally, TMM was corrected for BMI (TMM/BMI). The relationship between trunk muscle and whole-body sagittal alignment was analyzed for each age group (young-old group (60–74 years) and old–old group (>75 years)) and sex. A total of 281 (mean age 75.4 ± 6.7 years, 100 males and 181 females) were enrolled. The trunk muscle mass in both men and women significantly decreased with age. Regarding TMM/BMI, there was no significant difference in men, but there was a significant difference between females in the young-old and old–old groups (p < 0.001). TMM/BMI was significantly correlated with sagittal vertical axis (SVA) and knee flexion angle (KF) in both sexes. In females, TMM/BMI was significantly correlated with thoracic kyphosis in the young-old group, whereas in the old–old group, TMM/BMI was correlated with SVA, PI-LL, and KF. TMM was related to trunk anteverion and lower extremity alignment in both sexes. However, the relationship between TMM on alignment differs between sexes. Thoracic hyperkyphosis in young-old adults indicated a decrease in muscle mass, which may be a sign of future malalignment. [ABSTRACT FROM AUTHOR]

Background: Sagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.Method: Of the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5-years-old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2-C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA >4 cm, CL <0°, or T1S-CL ≧20°. We compared the cervical alignment of these patients with 121 age and gender matched volunteers (control group).Results: The prevalence of cervical spine deformity was significantly higher in the CLBP group than in the control group (20.7% vs. 10.7%, P = 0.034). The mean CL was smaller in the CLBP group than in the control group (16.1° vs. 21.4°, P = 0.002). The mean C2-7 SVA was 17.6 mm vs. 18.7 mm in the CLBP group and in the control group, respectively (P = 0.817). The mean T1S-CL was larger in the CLBP group than in the control group (9.1° vs. 3.5°, P < 0.001). Multivariate analysis showed that people with CLBP were more likely to have cervical deformities than people without CLBP (odds ratio 2.16, 95% confidence interval 1.006 to 4.637).Conclusions: This study results suggest that people with CLBP present with worse cervical sagittal alignment and higher prevalence of cervical spine deformities than age and gender matched volunteers with no CLBP. This means CLBP impacts cervical spine lesions negatively.Level Of Evidence: Ⅳ. [ABSTRACT FROM AUTHOR]

Background: Spinal shortening osteotomy (SSO) reduces the tension indirectly in the spinal cord and minimizes perioperative complications. However, the most effective and safe length to which the spine can be shortened is still unknown. In our practice, we use somatosensory-evoked potentials, motor-evoked potentials, and intraoperative ultrasonography when performing SSO. This study aimed to introduce the clinical outcomes of our SSO technique for tethered cord syndrome (TCS) in adults.Methods: This retrospective study included 7 adult patients (2 males and 5 females) with TCS treated between December 2010 and December 2018. The average age and average preoperative duration were 40 and 5 years, respectively. All patients received SSO with somatosensory-evoked potentials, motor-evoked potentials, and ultrasonography. After surgery, all patients were followed for an average of 4 years.Results: The mean operation time was 328 (284-414) min for SSO. The mean blood loss was 828 ml (501-1252 ml). Postoperative bony fusion was confirmed in all patients. Postoperative computed tomography (CT) demonstrated an average of 16 mm (11-20 mm) of spinal column shortening, compared with preoperative CT. Clinical improvements were obtained in all 7 cases, and there was no case of exacerbation. An indicator of shortening is that the ultrasonography gives pulsation and relaxation of the spinal cord. There were no abnormalities observed while monitoring the spinal cord.Conclusions: Spinal shortening should be done under somatosensory-evoked potentials, motor-evoked potentials, and intraoperative ultrasonography to obtain safe and sufficient shortening. [ABSTRACT FROM AUTHOR]

Background: Several studies indicated the influence of age and sex on spinal alignment using spino-pelvic radiographic parameters. However, information regarding the geometrical assessment of the sagittal spinal plane in the elderly population remains limited. This study aimed to determine the apices of lumbar lordosis and thoracic kyphosis, and spinal inflection point in elderly individuals and clarify the effect of age, sex, and pelvic incidence (PI) on sagittal geometry.Methods: In total, 440 volunteers (193 men; 247 women) were enrolled. The spino-pelvic radiographic parameters were measured. The apices of thoracic kyphosis and lumbar lordosis, and the inflection point where the vertebral curvature changes from kyphosis to lordosis were investigated. We analyzed the differences in the sagittal curve shape according to the sex, age, and PI magnitude.Results: On average, the apices of thoracic kyphosis and lumbar lordosis, and the inflection point were located at the levels of the T8/9 intervertebral disc, L3/4 disc, and L1 vertebra, respectively. Significant differences between men and women were observed with respect to the spino-pelvic parameters; however, the positions of the apices were significantly different only with respect to the lumbar apex offsets among individuals in their 70s. The inflectional point and apex of thoracic kyphosis among individuals aged >80 years were located significantly anteriorly and caudally in comparison to those among individuals aged <69 years. The apex of lumbar lordosis and the inflection point in individuals with high PI were located significantly anteriorly and cranially in comparison to those in individuals with low PI.Conclusions: The apices of thoracic kyphosis and lumbar lordosis, and the inflection point were located at the T8/9 intervertebral disc, L3/4 disc, and L1 vertebra, respectively. The shape of the sagittal spinal curve varied according to age and the magnitude of PI, and these findings cannot be evaluated using the conventional spino-pelvic parameters. Knowledge of standard geometrical spine shape could be useful for spinal deformity treatment in elderly patients. [ABSTRACT FROM AUTHOR]

Background: Degenerative lumbar scoliosis (DLS) is one of the most frequent spinal deformities of the aging spine. The purpose of our study was to clarify the independent predictors of pre-existing DLS progression and their influence on the health related quality of life (HRQOL).Methods: This study included 356 volunteers (127 men and 229 women; mean age, 72.2 years; follow-up period, 4 years) who underwent musculoskeletal screening. Standing whole-spine radiographic measurements included the Cobb angle of DLS and C7-center sacral vertical line (C7-CSVL; shift to the concave side of the DLS curve indicated a positive value). A baseline Cobb angle ≥10° indicated pre-existing DLS, and Cobb angle deterioration of ≥4° was considered DLS progression. For HRQOL assessment, the Oswestry Disability Index (ODI) was used. Pre-existing DLS cases were divided into progression and non-progression groups.Results: Among 93 cases (26.1%) with pre-existing DLS at baseline, 23 cases (pre-existing DLS progression group) showed DLS progression. The mean C7-CSVLs were 10.5 and -3.1 mm in the pre-existing progression and non-progression groups, respectively (p < 0.01). The optimal cutoff C7-CSVL length was 5 mm, with high sensitivity and specificity. Multivariate logistic regression analysis showed that a C7-CSVL ≥5 mm (odds ratio, 3.8; 95% CI: 1.42-10.34; p < 0.01) was independently associated with pre-existing DLS progression. ODI scores deteriorated significantly more in the pre-existing progression group than the non-progression group (+9.8% versus +3.9%; p < 0.05).Conclusions: Pre-existing DLS progression is associated with a shift to the concave side of C7-CSVL and influences HRQOL deterioration. It is important to assess coronal global alignment for prediction of a DLS progression. [ABSTRACT FROM AUTHOR]

Highlights • Sciatic nerve injury differentially affects lipid levels in DRGs and spinal cord. • An arachidonic acid-phosphatidylcholine, PC(16:0/20:4), increased in DRGs after sciatic nerve injury. • Two monounsaturated fatty acid-phosphatidylcholine, PC(16:0/18:1) and PC(18:0/18:1), decreased in DRGs after sciatic nerve injury. • Phosphatidic acid 36:2 decreased in DRGs after sciatic nerve injury. Abstract In the current study, we aimed to analyze the lipid changes in the dorsal root ganglion (DRG) after sciatic nerve transection (SNT) using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). We found that the arachidonic acid-containing phosphatidylcholine (AA-PC), PC(16:0/20:4) largely increased, while PC(16:0/18:1), PC(18:0/18:1) and phosphatidic acid (PA)(36:2) levels largely decreased in the DRG following nerve injury. Previous studies show that the increase in PC(16:0/20:4) was associated with neuropathic pain and that decrease in PC(16:0/18:1), PC(18:0/18:1), and PA(36:2) were due to producing lysophosphatidic acid (LPA), an initiator for neuropathic pain. These results suggest that the lipid changes in DRG after SNT could be the result of changes for the cause of neuropathic pain. Thus, blocking of LPA could be potential for treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: The Scoliosis Research Society-22r (SRS-22r) has been shown to be reliable, valid and responsive to change in patients with adult spinal deformity (ASD) undergoing surgery. The minimum clinically important difference (MCID) quantifies a threshold value of improvement that is clinically relevant to the patient. Health-related quality of life scores depend on age. The purpose of this study was to assess MCID threshold values stratified by age for SRS-22r domains in patients with ASD undergoing surgical correction.Methods: We identified a consecutive series of 184 Japanese ASD patients who completed the SRS-22r and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) preoperatively and 1 year postoperatively. Effectiveness as measured on the JOABPEQ was used as the anchor to determine MCID for the Function, Pain, and Mental health domains using receiver-operating-characteristic (ROC) curve analysis. We performed MCID analysis stratified by age (<70 or ≥70).Results: Mean preoperative SRS-22r Function score was 2.69 improving to 3.23 at postoperatively (p < 0.001). Mean preoperative SRS-22r Pain score was 3.04 improving to 3.78 at postoperatively (p < 0.001). Mean preoperative SRS-22r Mental health score was 2.72 improving to 3.25 at postoperatively (p < 0.001). There was a statistically difference in change in domain score between "not effective" and "effective" (p < 0.001). The ROC curve analysis methods yielded MCID values of 0.58 for Function, 0.55 for Pain, and 0.70 for Mental health domains. There was difference of MCID value for Function and Mental health domain between aged <70 and ≥70; 0.78 and 0.55 for Function; 0.70 and 0.48 for Mental health.Conclusion: Results of this study showed that MCID threshold values for SRS-22 Function and Mental health domains in older than 70 was lower than in younger than 70, potentially implying that older patients have lower expectation. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) radiation is one of the most important environmental factors involved in the pathogenesis of skin aging and cancer. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species, and cellular antioxidants act to prevent the occurrence and reduce the severity of UV-induced skin disorders. Transcription factor NF-E2-related Factor 2 (Nrf2) and its cytoplasmic anchor protein Kelch-like-ECH-associated protein 1 (Keap1) are central regulators of the cellular antioxidant response. In this study, we investigated the effects of UV irradiation on the activation of Nrf2 in dermal fibroblasts. We found that UVA irradiation, but not UVB, causes nuclear translocation and accumulation of Nrf2 by a factor of 6.5 as compared with unirradiated controls. The nuclear accumulation of Nrf2 induced by UVA was enhanced by the photosensitizer hematoporphyrin. To evaluate the protective role of Nrf2 against UVA radiation, we examined UVA-induced apoptosis using dermal fibroblasts derived fromnrf2orkeap1gene knockout mice. Whereas disruption ofnrf2increased the number of apoptotic cells following UVA irradiation by 1.7-fold, disruption ofkeap1decreased the apoptotic cell number by half as compared with wild-type controls. These findings thus demonstrate that the Nrf2–Keap1 pathway plays an important role in the protection of the skin against UVA irradiation. [ABSTRACT FROM AUTHOR]

Loricrin is a major component of the epidermal cornified cell envelope, and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific suppression of loricrin gene expression in undifferentiated keratinocytes as well as its activation in differentiated keratinocytes. We identified a negative regulatory sequence element in the first intron of the mouse loricrin gene involved in suppression of loricrin gene expression in undifferentiated keratinocytes. A database search indicated that this sequence contained the putative inverted Yin-Yang 1 (YY1)-binding motif. Constructs with point mutations in the putative YY1-binding motif showed increased reporter activity, indicating that YY1 negatively regulates loricrin gene transcription. Co-transfection experiments using a YY1 expression vector revealed that YY1 represses loricrin promoter activity. Western blotting and immunohistochemical analyses indicated that YY1 is more abundant in undifferentiated than in differentiated keratinocytes. These findings suggest that YY1 contributes to specific loricrin gene expression in differentiated keratinocytes by suppression of its transcription in undifferentiated keratinocytes. Furthermore, we demonstrated that forced expression of YY1 in differentiated keratinocytes results in specific downregulation of expression of other early and late differentiation markers. [ABSTRACT FROM AUTHOR]