Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen-activated protein kinase and protein kinase B pathways.

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

Oral cancer: A multicenter study.

BACKGROUND: To determine the prevalence and clinicopathologic features of the oral cancer patients. MATERIAL AND METHODS: Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. RESULTS: Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. CONCLUSIONS: Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

Estimating the Basal metabolic rate from fat free mass in individuals with motor complete spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: This study aimed to validate the existing basal metabolic rate (BMR) predictive equations that include fat free mass (FFM) as an independent variable and, based on the FFM assessment, to develop a new SCI population-specific equation. SETTING: Outpatient clinic in a general hospital. METHODS: Our study group was formed of 50 individuals with chronic motor complete SCI: 27 patients with tetraplegia and 23 with paraplegia. Both BMR and FFM values were measured by indirect calorimetry (IC) and the whole-body dual energy X-ray absorptiometry, respectively. The BMR values measured by IC were compared with the values estimated from the Cunningham equation. Multiple linear regression analysis was performed to develop a new FFM-based, BMR predictive equation. RESULTS: The mean value of BMR measured by IC was 1274.8 (s.d.=235.2) kcal day-1. The intra-class correlation coefficient (ICC) between values measured by IC and estimated from the Cunningham equation was 0.845 and the limits of agreement ranged from -30.6 to 241.3 kcal. SCI population specific BMR predictive equation was developed; BMR (kcal day-1)=24.5 × FFM (kg)+244.4. The newly developed equation showed ICC of 0.866 with the limits of agreement from -229.0 to 233.1 kcal day-1. CONCLUSIONS: A considerable bias from the BMR values measured by IC was still observed, which warrants clinical consideration when applying FFM-based BMR prediction equations to individuals with SCI.

Histopathological and scanning electron microscopy findings of retrieved porous polyethylene implants.

Porous polyethylene (PPE) implants are biocompatible alloplastic materials commonly used for facial augmentation. However, the effect of sub-periosteal PPE application on the surrounding tissues has not been analyzed clearly. This report documents the case of a 22-year-old woman who underwent peri-alar augmentation with PPE to improve midface retrusion. Although no infection or inflammation occurred at the surgical site, the patient requested removal of the PPE implant for aesthetic reasons alone at 1 year after the surgery. The removed implant was subjected to histological and morphological evaluation using conventional histological staining and scanning electron microscopy (SEM). Histopathological staining revealed bone ingrowth into the pores of the implant near the boundary with the host bone. Little evidence of a foreign body reaction was observed. SEM revealed densely arranged collagen fibres and osteoblastic cells in the pores. Moreover, the outer surface of the PPE implant in contact with the periosteum showed fibrous tissue ingrowth, leading to tissue adhesion. These findings confirm bone ingrowth into the PPE pore structure in humans.

Severe spasticity in lower extremities is associated with reduced adiposity and lower fasting plasma glucose level in persons with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To investigate the effects of severe lower extremity spasticity on anthropometric dimensions, body composition and metabolic profiles in persons with chronic motor complete spinal cord injury (SCI). SETTING: Outpatient clinic. METHODS: Fifty-five of the 61 participants were divided into two groups (no or mild spasticity group, 28; severe spasticity group, 27) based on the assessment of the extensor muscle spasticity according to the modified Ashworth scale. Anthropometric dimensions (waist circumference (WC), waist-to-height ratio (WtHR)), body composition (fat mass (FM), body fat percentage (BFP), fat-free mass (FFM), fat-free mass percentage (FFMP), bone mineral density (BMD)) and metabolic profiles (leptin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c)) were compared between the two groups with different degree of spasticity. RESULTS: Spasticity of the extensor muscle group negatively correlated with BFP (r=-0.458, P<0.001). Patients with severe spasticity showed a lower WC and WtHR than those in the no or mild spasticity group (P=0.038, P=0.006, respectively). The FM, BFP, leptin and FPG of the severe spasticity group were significantly lower than those of the patients in the no or mild spasticity group (P=0.003, P<0.001, P<0.001 and P=0.037, respectively). However, no differences in BMD, total cholesterol, LDL, HDL, TG and HbA1c were observed between the groups. CONCLUSIONS: The results of this study suggest that severe spasticity in lower extremities is associated with reduced adiposity and lower FPG levels in persons with chronic motor complete SCI.

Sexual activity and sexual satisfaction in Korean men with spinal cord injury.

STUDY DESIGN: A cross-sectional survey. OBJECTIVES: The aim of this study was to identify and assess the sexual activity and perceived sexual satisfaction of Korean males with spinal cord injury (SCI) and to identify factors influencing sexuality and satisfaction. SETTING: Community residents with SCI. METHODS: A total of 139 male participants with SCI in Korea were eligible for inclusion in this study. All participants completed a face-to-face interview regarding sexuality and satisfaction, as well as structured questionnaires including items on socioeconomic factors, medical conditions and rehabilitation services. RESULTS: A total of 90 participants (65%) were engaged in sexual activity. A period of 21-25 years since SCI (compared with the initial 5 years since SCI) and an experience of direct sexual rehabilitation education were positively associated with sexual activity. Among 90 sexually active males with SCI, 8 (8.9%) and 56 (62.2%) were sexually satisfied and unsatisfied, respectively. Lower levels of education were strongly correlated with sexual dissatisfaction. CONCLUSION: Korean males with SCI showed low levels of satisfaction regarding sexual activities. Results showed that socioeconomic factors (e.g., state of employment and direct person-to-person sexual counseling services) had a greater impact on sexual activity than the degree of physical impairment. Notably, the educational background was the most influential factor on sexual satisfaction.

Interrater reliability of the Korean version of the International Spinal Cord Injury Basic Pain Data Set.

OBJECTIVES: To provide a Korean translation of the International Spinal Cord Injury Basic Pain Data Set (ISCIBPDS) and evaluate the interrater reliability of the translated version. SETTING: Survey of community-dwelling people with spinal cord injury (SCI) in South Korea. METHODS: The initial translation was performed by two translators with an in-depth knowledge of SCI, and was then checked by another person with a similar background. A total of 115 SCI participants (87 men, 28 women; 48.4±14.1 years) were evaluated using the Korean version of the ISCIBPDS by two different raters. Intraclass correlation coefficient (ICC) or Cohen's kappa (κ) was used for analysis. RESULTS: All 115 participants had at least one pain problem on both surveys. Seventeen (14.8%) participants described their pain as a single pain problem to one rater while reporting the same pain as two or more different pain problems to the other rater. Twenty-two (19.1%) other participants reported their pain problems in a different order of severity on the surveys. The Korean version of the ISCIBPDS had acceptable interrater reliability, except in the 'limit activities (how much do you limit your activities in order to keep your pain from getting worse?)' item (ICC=0.318). CONCLUSION: Provision of criteria for pain separation may facilitate the consistent application of ISCIBPDS. In addition, the ISCIBPDS, which evaluated pain problems separately, reflected the multiple and complex characteristics of SCI-related pain; this was a strength of this data set.

Contribution of mesenchymal proliferation in tooth root morphogenesis.

In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig's epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.

Suicidal ideation in Korean persons with spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To investigate the prevalence of suicidal ideation and attempt in Korean persons with spinal cord injury (SCI) and the factors related with suicidal ideation in comparison with a control group (CG). SETTINGS: Community-dwelling persons with chronic SCI in Korea. METHODS: A total of 382 persons with chronic SCI and 1104 able-bodied persons randomly selected from the general population and matched for age, sex and education level were compared. Suicidal ideation and attempt were recorded positive if the subjects had that experience during the past year. Psychosocial variables and injury-related factors were also evaluated. RESULTS: Suicidal ideation was found in 34.8% (127/365) of SCI persons and 10.4% (115/1104) in the CG (P<0.001). The rate of suicidal attempt among those with suicidal ideation was 17.3% (22/127) in SCI and 8.7% (10/115) in CG (P=0.048). Multiple logistic regression revealed that SCI itself (odds ratio (OR) 2.865) was a significant risk factor of suicidal ideation. However, completeness of injury and injury level were not significantly associated with suicidal ideation. Depressive mood (OR 11.194, P<0.001) and female gender (OR 3.706, P<0.001) were significant risk factors of suicidal ideation in the SCI group with a predictive percentage of 77.5%. CONCLUSION: Suicidal ideation was more frequent among Korean persons with SCI compared with able-bodied peers and closely related to psychosocial adjustment. The results support the need for active intervention to prevent suicide regardless of injury severity.

Application of transanal irrigation for patients with spinal cord injury in South Korea: a 6-month follow-up study.

STUDY DESIGN: A 6-month follow-up study. OBJECTIVES: To investigate the outcome of transanal irrigation (TAI) in patients with spinal cord injury (SCI) and to identify factors significantly related to clinical success. SETTING: Survey for community-dwelling patients with SCI in South Korea. METHODS: Between December 2010 and March 2012, TAI was initiated with 52 patients (41 men; age: 44.5±11.0 years) with neurogenic bowel dysfunction (NBD). At 1, 3 and 6 months after initiation, a telephone interview was conducted. Data were collected on patient-specific bowel management and TAI performance as a new procedure. RESULTS: Only 18 patients (34%) used TAI for at least 6 months, which was a lower compliance rate than similar studies in some European countries. Relative to the compliant group, the noncompliant group contained a higher proportion of tetraplegia than paraplegia (P=0.031), and a higher proportion dependent on physical help (P=0.034). In all, 33 of the 52 patients (63.5%) complained of practical problems with the TAI procedure such as expulsion of the rectal catheter. Fifteen patients (28.8%) presented with adverse effects. The incidence of practical problems or adverse effects did not alter the frequency of patient-reported successful outcome. CONCLUSION: Korean participants showed a relatively lower compliance rate with TAI. We conclude that TAI, combined with adequate patient instruction and physical assistance, has potential as a management tool for NBD in Korea.

Management of bowel dysfunction in the community after spinal cord injury: a postal survey in the Republic of Korea.

STUDY DESIGN: A cross-sectional postal survey. OBJECTIVES: To describe defecation stimulation methods and their outcomes, and to investigate the impact of bowel dysfunction on the quality of life (QoL) in community-dwelling persons with spinal cord injury in South Korea. SETTING: Community-based, Korea. METHODS: A cross-sectional postal survey was conducted. Questionnaires were sent to 459 chronic spinal cord injury (SCI) patients who were registered as members of the Korean Spinal Cord Injury Association. Defecation stimulation methods and their outcomes, the impact of bowel dysfunction on the QoL were investigated. RESULTS: A total of 388 subjects (44.5±10.8 year of age; men, 76.0%; duration of time since the onset of SCI, 14.2±9.5 years) responded. Bowel-related general, social and home QoL deterioration was found in >60%. Suppositories (Supp) were most frequently used, followed by digital rectal stimulation (DRS). The mini enema (ME), which is exclusively used in Korea, was utilized in 18.8%. A defecation time of 30 min was more frequently reported in patients who stimulated defecation with Supp than in those who used DRS. CONCLUSIONS: The use of MEs and warm-water irrigations were newly identified in Korea. Bowel care-related factors that greatly deteriorate the QoL were fecal incontinence, time in one defecation >60 min, perianal skin problem, flatus incontinence and hemorrhoids. Alleviating these factors might help to improve the QoL. In particular, stimulation methods to reduce time for defecation might be recommended to persons with chronic SCI.

Polymorphisms in the Matrilin-1 gene and risk of mandibular prognathism in Koreans.

Previous linkage analysis of an Asian population proposed possible candidate genes for mandibular prognathism, such as Matrilin-1 (cartilage matrix protein). To investigate the association between the single-nucleotide polymorphisms (SNPs) in Matrilin-1 and mandibular prognathism, we investigated three sequence variants (-158 T>C, 7987 G>A, 8572 C>T) in 164 mandibular prognathism patients and 132 control individuals with a normal occlusion. The results showed that the 8572 TT genotypes in Matrilin-1 showed increased risk of mandibular prognathism (OR = 9.28, 95% Cl = 1.19~197.57, P < 0.05), whereas the 7987 AA genotype showed a protective effect for mandibular prognathism (OR = 0.16, 95% Cl = 0.05~0.47, P < 0.05). Genotyping results showed that the Matrilin-1 polymorphism haplotype TGC (ht4; 158T, 7987G, and 8572C alleles) had a pronounced risk effect for mandibular prognathism compared with controls (OR = 5.16, 95% Cl = 2.03~13.93, P < 0.01). The results suggest that polymorphisms in Matrilin-1 could be used as a marker for genetic susceptibility to mandibular prognathism.

Therapeutic trial of fluoroscopic interlaminar epidural steroid injection for axial low back pain: effectiveness and outcome predictors.

BACKGROUND AND PURPOSE: An ESI for managing LBP is one of the most commonly performed interventions. The purpose of this observational study was to assess the effect of a therapeutic trial of a fluoroscopic interlaminar ESI for axial LBP and to analyze the outcome predictors. MATERIALS AND METHODS: All patients who received an interlaminar ESI for axial LBP at our facility in 2007 and 2008 were included. Initial short-term follow-up was done at <1 month after ESI. ESI was considered effective if patients had a reduction of >50% in their pain scores. In July 2009, telephone interviews were conducted by using formatted questions including the NASS patient-satisfaction index. The symptom-free interval was computed by the Kaplan-Meier method. Outcome predictors such as age, sex, duration of LBP, and MR imaging findings were statistically analyzed by the Mann-Whitney U and the Fisher exact tests. RESULTS: Eighty-one patients (male/female = 16:65; mean age, 49.9 years; range, 17-77 years) were included in the study. The interlaminar ESI was effective in 63 of the 81 patients (77.8%) at initial short-term follow-up. For the 63 patients in whom ESI was effective, the median symptom-free interval was 154 days (95% CI, 96-212 days). Among 68 patients for whom telephone interviews were possible, 44 patients (64.7%) replied positively to the NASS patient satisfaction index (NASS patient-satisfaction index, 1 or 2). There were no significant outcome predictors. CONCLUSIONS: The therapeutic trial of a fluoroscopic interlaminar ESI was effective for axial LBP without significant outcome predictors.

Comparison between nerve conduction studies and current perception threshold test in carpal tunnel syndrome.

AIM OF STUDY: Nerve conduction studies (NCS) only test large myelinated A(alpha) or A(beta) nerve fibers, whereas the current perception threshold (CPT) test has been suggested to evaluate a wide range of nerve fibers (A(beta), A(delta) and C). This study was undertaken to compare CPT and the standard NCS test by Bland's severity scale with the patient-based measurement of symptoms and functional status of the hand by Boston CTS questionnaire assessment. PATIENTS AND METHODS: We performed NCS and CPT on 31 patients (mean age 54.6+/-11.7 years; 31-79 years) with clinical diagnosis of CTS. NCS severity was classified according to Bland's scale and CPT was measured at 2000, 250 and 5 Hz and severity was graded between 0 and 12. Two-tailed Spearman's correlation analysis was performed to assess correlations between Boston questionnaire score and Bland's severity scale and CPT total score. RESULTS: The results showed that Bland's scale, based on NCS, had more significant correlations with symptoms (Spearman's rho=0.402, p=0.002) and function (rho=0.400, p=0.001) than CPT total scores (rho=0.200, p=0.135; rho=0.234, p=0.069). In CPT, only score measure at 2000 Hz showed a significant correlation with Boston CTS questionnaire scores (with symptom rho=0.308, p=0.020; with function rho=0.302, p=0.018), whereas those measured at 250 Hz and 5 Hz did not (p>0.05). CONCLUSION: Though CPT may have a supplementary role in the diagnosis of CTS, NCS better reflects patients' symptoms and functions than CPT on the patient's perspective.

Substance P regulates macrophage inflammatory protein 3alpha/chemokine C-C ligand 20 (CCL20) with heme oxygenase-1 in human periodontal ligament cells.

Although substance P (SP), a potent proinflammatory peptide, is involved in inflammation and immune responses, the effect of SP on the expression of macrophage inflammatory protein 3alpha[MIP-3alpha, chemokine C-C ligand 20 (CCL20)] in periodontal ligament (PDL) cells is unknown. Equally enigmatic is the link between SP, the stress protein heme oxygenase-1 (HO-1), and CCL20 production. We investigated whether SP induces the release of chemokine CCL20 from immortalized PDL (IPDL) cells, and further clarify SP-mediated pathways. We also examined the relationship between HO-1 and CCL20 by treating PDL cells with SP. Incubating IPDL cells with SP increased expression of CCL20 mRNA and CCL20 protein in a dose-time-dependent manner. Highly selective p38 and extracellular-regulated kinase 1/2 (ERK1/2) inhibitors abrogated SP-induced expression of CCL20 in IPDL cells. SP is also responsible for initiating phosphorylation of IkappaB, degradation of IkappaB and activation of nuclear factor (NF)-kappaB. SP induced expression of HO-1 in both a concentration- and time-dependent manner, and CCL20 reflected similar patterns. The inductive effects of SP on HO-1 and CCL20 were enhanced by HO-1 inducer hemin and the membrane-permeable guanosine 3',5'-monophosphate (cGMP) analogue 8-bromo-cGMP. Conversely, this pathway was inhibited by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) and the selective inhibitor of guanylate cyclase, 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one (ODQ). We report herein the pathway that connects SP along with other modulators of neuroimmunoregulation to the induction of HO-1 and the inflammatory mediator macrophage inflammatory protein (MIP)-3alpha/CCL20 in IPDL cells, which play an important role in the development of periodontitis or inflammation during orthodontic tooth movement.

Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-kappaB and p38 MAPK in HMC-1 human mast cell line.

OBJECTIVE AND DESIGN: Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce production of pro-inflammatory cytokines with immune regulatory properties. We investigated the effect of quercetin on the expression of pro-inflammatory cytokines in human mast cell line, HMC-1. METHODS: HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 (PMACI). RESULTS: Quercetin decreased the gene expression and production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 in PMACI-stimulated HMC-1 cells. Quercetin attenuated PMACI-induced activation of NF-kappaB and p38 mitogen-activated protein kinase. CONCLUSION: Our study provides evidence that quercetin may suitable for the treatment of mast cell-derived allergic inflammatory diseases.

Identification of novel RANK polymorphisms and their putative association with low BMD among postmenopausal women.

INTRODUCTION: Bone mineral density (BMD) is the major factor for determining bone strength, which is closely correlated to osteoporotic fracture risk and is largely determined by multiple genetic factors. The RANK (TNFRSF11A), receptor for RANKL, is a member of the tumor necrosis factor receptor (TNFR) superfamily and plays a central role in osteoclast development. METHODS: In order to investigate the effects of RANK polymorphism on BMD and osteoporosis, we directly sequenced the RANK gene in 24 Korean individuals and identified 25 sequence variants. Eleven of these polymorphisms were selected and genotyped in a larger-scale study of postmenopausal women (n = 560). Areal BMD (g/cm(2)) of the anterior-posterior lumbar spine and the nondominant proximal femur were measured using dual-energy X-ray absorptiometry. RESULTS: We found that two intronic polymorphisms in the RANK gene [RANK + 34863G > A (rs12458117) and RANK + 35928insdelC (new polymorphism found in this study) in intron 6] were significantly associated with the BMD of the lumbar spine, i.e., rare alleles were significantly associated with low BMD of the lumbar spine among Korean postmenopausal women (p = 0.04 and 0.02, respectively). These polymorphisms were also associated with low BMD of proximal femur sites, including Ward's triangle, trochanter, and total femur. Our results suggest that +34863G > A and +35928insdelC polymorphisms in RANK are possible genetic factors for low BMD in postmenopausal women.

Depressive symptoms of patients using clean intermittent catheterization for neurogenic bladder secondary to spinal cord injury.

STUDY DESIGN: Prospective, cross-sectional study, based on cases of spinal cord injury (SCI). SETTING: Three outpatient medical departments in Seoul, Korea. OBJECTIVES: To assess depressive symptoms in patients on clean intermittent catheterization after SCI. METHODS: In total, 102 subjects (68 males and 34 females, mean age 39.5 with a range of 18-75 years) were included in the primary analysis. A control group of 110 was selected from the routine health checkup. All subjects completed the Beck Depression Inventory (BDI). RESULTS: For patients and controls, the average total BDI scores were 20.3+/-1.0 and 11.4+/-0.5, respectively (P<0.001). With regard to severity of depression among patient groups, three (3.0%) reported normal; four (3.9%) reported mild to moderate depression; 24 (23.5%) reported moderate to severe depression; and 71 (69.6%) reported severe depression. On the multivariate logistic regression analysis, a positive association with the risk of depression was observed in gender and type of catheterization. Female patients had a 3.8-fold higher risk (odds ratio (OR) 13.83; 95% confidence interval (CI) 1.42-10.31; P=0.008) of depression than male patients. In the same model, patients who were unable to perform catheterization independently had a 4.6-fold higher risk (OR 4.62; 95% CI 1.67-12.81, P=0.003) of depression than those who were able to perform self-catheterization. CONCLUSIONS: The results demonstrate that the patients with neurogenic bladder secondary to SCI have higher degrees of depression than normal population. In addition, our findings also suggest that depression is closely related to gender and patient's ability to perform self-catheterization.

Constitutively active PTH/PTHrP receptor in odontoblasts alters odontoblast and ameloblast function and maturation.

Parathyroid hormone (PTH)-related protein (PTH-rP) is an important autocrine/paracrine attenuator of programmed cell differentiation whose expression is restricted to the epithelial layer in tooth development. The PTH/PTHrP receptor (PPR) mRNA in contrast is detected in the dental papilla, suggesting that PTHrP and the PPR may modulate epithelial-mesenchymal interactions. To explore the possible interactions, we studied the previously described transgenic mice in which a constitutively active PPR is targeted to osteoblastic cells. These transgenic mice have a vivid postnatal bone and tooth phenotype, with normal tooth eruption but abnormal, widened crowns. Transgene mRNA expression was first detected at birth in the dental papilla and, at 1 week postnatally, in odontoblasts. There was no transgene expression in ameloblasts or in other epithelial structures. Prenatally, transgenic molars and incisors revealed no remarkable change. By the age of 1 week, the dental papilla was widened, with disorganization of the odontoblastic layer and decreased dentin matrix. In addition, the number of cusps was abnormally increased, the ameloblastic layer disorganized, and enamel matrix decreased. Odontoblastic and, surprisingly, ameloblastic cytodifferentiation was impaired, as shown by in situ hybridization and electron microscopy. Interestingly, ameloblastic expression of Sonic Hedgehog, a major determinant of ameloblastic cytodifferentiation, was dramatically altered in the transgenic molars. These data suggest that odontoblastic activation of the PPR may play an important role in terminal odontoblastic and, indirectly, ameloblastic cytodifferentiation, and describe a useful model to study how this novel action of the PPR may modulate mesenchymal/epithelial interactions at later stages of tooth morphogenesis and development.

Differential expression patterns of Runx2 isoforms in cranial suture morphogenesis.

Runx2 (previously known as Cbfal/Pebp2alphaA/AML3), a key transcription factor in osteoblast differentiation, has at least two different isoforms using alternative promoters, which suggests that the isoforms might be expressed differentially. Haploinsufficiency of the Runx2 gene is associated with cleidocranial dysplasia (CCD), the main phenotype of which is inadequate development of calvaria. In spite of the biological relevance, Runx2 gene expression patterns in developing calvaria has not been explored previously, and toward this aim we developed three probes: pRunx2, which comprises the common coding sequence of Runx2 and hybridizes with all isoforms; pPebp2alphaA, which specifically hybridizes with the isoform transcribed with the proximal promoter; and pOsf2, which hybridizes with the isoform transcribed with the distal promoter. These probes were hybridized with tissue sections of mouse calvaria taken at various time points in development. Runx2 expression was localized to the critical area of cranial suture closure, being found in parietal bones, osteogenic fronts, and sutural mesenchyme. Pebp2alphaA and Osf2 showed tissue-specific expression patterns. The sites of Pebp2alphaA expression were almost identical to that of pRunx2 hybridization but expression was most intense in the sutural mesenchyme, where undifferentiated mesenchymal cells reside. The Osf2 isoform was strongly expressed in the osteogenic fronts, as well as in developing parietal bones, where osteopontin (OP) and osteocalcin (OC) also were expressed. However, in contrast to Pebp2alphaA, Osf2 expression did not occur in sutural mesenchyme. Pebp2alphaA also was expressed prominently in primordial cartilage that is found under the sutural mesenchyme and is not destined to be mineralized. Thus, Osf2 isoforms contribute to events later in osteoblast differentiation whereas the Pebp2alphaA isoform participates in a wide variety of cellular activities ranging from early stages of osteoblast differentiation to the final differentiation of osteoblasts.