Differences in Pilon Fractures According to Ipsilateral Fibular Injury Patterns: A Clinical Computed Tomography-Based Mapping Study.

Background: Preoperative verification of fracture morphology is essential for determining the definitive fixation strategy in the management of a pilon fracture. This study aimed to determine the correlation between fibular injury patterns and fracture morphologies and introduce clinical implications. Methods: Computed tomography scans of 96 pilon fractures were retrospectively analyzed and divided into three types: intact fibula, simple fracture, and multifragment fracture. The principal fracture line and comminution zones were illustrated on a plafond template and diagrammatized on a 6 × 6 grid using PowerPoint software as fracture mapping. Correlations between fibular injury patterns and fracture morphologies, including comminution zones and principal fracture lines, were analyzed. Results: The thickest comminution zone was most often located in the anterolateral quadrant. According to fibular injury patterns, the comminution zone of the multifragment group was placed two grids more lateral than that of other groups. Lateral exits of the principal fracture line in the multifragment group were much more concentrated within the fibular incisura. Conclusions: In pilon fractures, a more complex fibular fracture pattern was related to the valgus position. Moreover, the articular fracture pattern of pilon fractures differed according to coronal angulation and fibular fracture pattern. These differences should influence the operative approach and placement of the plate.

The Effect of Apple-Derived Nanovesicles on the Osteoblastogenesis of Osteoblastic MC3T3-E1 Cells.

Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5 µg/mL apple NVs-treated group. In addition, the concentrarion of mineralized nodules was significantly increased in the apple NVs-treated groups. Furthermore, apple NVs increased the expression of the genes and proteins associated with osteoblast growth and differentiation, such as Runx2, ALP, OPN, and BMP2/4, which further activated ERK- and JNK-related mitogen-activated protein kinase signaling. These results demonstrate that apple NVs have a potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells through regulating the BMP2/Smad1 pathways.

Plum-Derived Exosome-like Nanovesicles Induce Differentiation of Osteoblasts and Reduction of Osteoclast Activation.

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 µg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.

Implications of the Overlapping Degree Between Proximal Fibula and Tibia for Placing the Optimal Syndesmotic Screw: A Virtual Cadaveric Study.

BACKGROUND: To determine the optimal direction of the syndesmotic screw and to introduce a consistent landmark for practical application by analyzing three-dimensional (3D) modeling and virtual implantation. METHODS: A total of 105 cadaveric lower legs (50 males and 55 females; average height, 160.6 ± 7.1 cm) were used to reconstruct a 3D model by using the Mimics® software and the joint morphology was evaluated. Syndesmotic cylinders (Ø3.5 mm/Length 100 mm) were transversely placed in the proximal end of the incisura fibularis for simulating screw fixation. The tibial proximal cylinder, which was tangent to the posterior tibial condyles, was traced and the angle between the two cylinders was measured as the tibial torsion angle (TTA). After rotating the syndesmotic cylinder parallel to the ground, the overlapping degree between the proximal fibula and tibia was assessed as a radiologic indicator. RESULTS: Concerning tibial torsion, the TTA was an average of 36.7° (range, 17.2°-54.4°; SD, 8.78) When the syndesmotic cylinder was rotated to be parallel to the ground, the proximal fibula had nonlinear or linear overlap with the lateral border of the tibia, regardless of the joint morphology. In this non-overlapping view, three Weber's indices for normal fibular length could be better visualized than the mortise view. CONCLUSION: The syndesmotic cylinder in the proximal end of the incisura fibularis could be consistently placed parallel to the ground by internally rotating the tibia until there was a nonlinear or linear overlap between the proximal fibula and the tibia, regardless of the joint morphology.

Correction to: Implications of the Overlapping Degree Between Proximal Fibula and Tibia for Placing the Optimal Syndesmotic Screw: A Virtual Cadaveric Study.

[This corrects the article DOI: 10.1007/s43465-021-00437-y.].

Plum Prevents Intestinal and Hepatic Inflammation in the Acute and Chronic Models of Dextran Sulfate Sodium-Induced Mouse Colitis.

SCOPE: Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a chronic recurrent inflammatory disease of the digestive tract and increases the risk of colon cancer. METHOD AND RESULTS: This study evaluates the effects of dietary intervention with freeze-dried plum (FDP), a natural antioxidant and anti-inflammatory fruit with no toxicity on dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis in a mouse model and studies the molecular mechanisms of protection through the gut-liver axis. The results show that FDP decreases the levels of inflammatory mediators, which is a nitrative stress biomarker in both acute and chronic models. FDP markedly reduces DSS-induced injury to the colonic epithelium in both acute and chronic models. In addition, FDP significantly decreases the levels of pro-oxidant markers such as CYP2E1, iNOS, and nitrated proteins (detected by anti-3-NT antibody) in DSS-induced acute and chronic colonic injury models. Furthermore, FDP markedly reduces markers of liver injury such as serum ALT/AST, antioxidant markers, and inflammatory mediators in DSS-induced acute and chronic colonic injury. CONCLUSION: These results demonstrate that the FDP exhibits a protective effect on DSS-induced acute and chronic colonic and liver injury through the gut-liver axis via antioxidant and anti-inflammatory properties.

Is the popliteus tendon always inserted antero-inferiorly 18.5 mm from the lateral collateral ligament of the femur? Magnetic resonance imaging and cadaveric evaluations.

BACKGROUND: The aim of this study was to analyze the locations of the femoral attachments of the popliteus tendon (PT) and lateral collateral ligament (LCL) via magnetic resonance imaging (MRI) and cadaveric dissection in a Korean population and compare with literature standards to determine whether variability exists. METHODS: We retrospectively analyzed knee MRIs from 87 cases selected from January 2017 to December 2018. The relationship between the femoral attachment of PT and LCL was analyzed by MRI using PACS and Image J. In addition, the femoral attachments of each structure were identified and marked in 14 unpaired human cadaveric knees. Three-dimensional models were reconstructed, and the surface area, location and distances were analyzed. RESULTS: On MRI, the femoral attachment of PT was located at mean distances of 0.89 mm posterior and 9.35 mm inferior to the LCL femoral attachment. We identified three groups of PT locations relative to the LCL on MRI evaluation: parallel (63%), posterior (29%), and anterior (8%). On cadaveric evaluation, the femoral attachment of the PT was located at mean distances of 0.77 mm posterior and 8.90 mm inferior to the LCL femoral attachment. We also identified three groups of PT locations relative to the LCL on cadaveric evaluation: parallel (43%), posterior (36%), and anterior (21%). CONCLUSIONS: Based on both MRI and cadaveric evaluations in a Korean population, the femoral attachment of the PT is located just distal to and posterior to the LCL. The differences between the centroids of the femoral attachments of the two structures was approximately 9.7 mm, suggesting that racially based anatomical differences of the posterolateral corner may exist.

Effectiveness and Safety of the Korean Medicine Senior Health Promotion Program Using Herbal Medicine and Acupuncture for Mild Cognitive Impairment: A Retrospective Study of 500 Patients in Seoul, Korea.

BACKGROUND: The management of mild cognitive impairment (MCI) is becoming increasingly important. The Korean Medicine Senior Health Promotion Program (KSHPP) was developed in 2016, and it has been in use to date. This study aimed to assess the effectiveness of KSHPP using herbal medicine and acupuncture for treating MCI and the safety of herbal medicine using liver and renal function tests. METHODS: We retrospectively reviewed the medical records of the participants with MCI. We assessed the Korean version of the Montreal Cognitive Assessment (MoCA-K), the Mini-Mental State Examination-Dementia Screening (MMSE-DS), and the Geriatric Depression Scale Short Form-Korea version (GDSSF-K) scores before and after KSHPP to determine its effectiveness. To evaluate its safety, the liver and renal function tests were conducted before and after herbal treatment. RESULTS: We enrolled 1002 participants, and 500 participants satisfied the inclusion criteria. Of 500 patients, 364 (72.8%) were depressed and 136 (27.2%) were not. The mean MoCA-K score significantly increased by 2.77 for the entire sample and 3.22 for the depressed sample (all P < 0.0001). The mean MMSE-DS score significantly increased by 2.19 for the entire sample and 2.51 for the depressed sample (all P < 0.0001); the mean GDSSF-K score significantly decreased by 1.73 for the entire sample and 2.68 for the depressed sample (all P < 0.0001). CONCLUSIONS: Our findings suggest that Korean medicine interventions can improve cognitive function and depression symptoms in patients with MCI. In addition, the results of the liver and renal function tests were analyzed as surrogate outcomes to assess the safety of herbal medicine. Based on these results, we expect that Korean medicine interventions can promote the cognitive and mental health of seniors. However, as there were several study limitations, particularly study design, practice effect, and short follow-up, these results must be interpreted with caution. We need a further long-term study with a rigorous design to retain confidence in the effectiveness and safety of KSHPP.

Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress.

Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.

Expansion of chromosome territories with chromatin decompaction in BAF53-depleted interphase cells.

Chromosomes are compartmentalized into discrete chromosome territories during interphase in mammalian cells. A chromosome territory is generated by the tendency of chromatin to occupy the smallest shell volume, which is determined by the polymeric properties and interactions of the internal meshwork of the chromatin fiber. Here, we show that BAF53 knockdown by small interfering RNA interference led to the expansion of chromosome territories. This was accompanied by a reduction in chromatin compaction, an increase in the micrococcal nuclease sensitivity of the chromatin, and an alteration in H3-K9 and H3-K79 dimethylation. Interestingly, the BAF53 knockdown cells suffer a cell cycle defect. Despite the significant irregularity and decompaction of the polynucleosomes isolated from the BAF53 knockdown cells, the chromatin loading of H1 and core histones remained unaltered, as did the nucleosome spacing. The histone hyperacetylation and down-regulation of BRG-1, mBrm, and Tip49, the catalytic components of the SWI/SNF complex and the TIP60 complex, respectively, did not expand chromosome territories. These results indicate that BAF53 contributes to the polymeric properties and/or the internal meshwork interactions of the chromatin fiber probably via a novel mechanism.

Down-regulation of nucleosomal binding protein HMGN1 expression during embryogenesis modulates Sox9 expression in chondrocytes.

We find that during embryogenesis the expression of HMGN1, a nuclear protein that binds to nucleosomes and reduces the compaction of the chromatin fiber, is progressively down-regulated throughout the entire embryo, except in committed but continuously renewing cell types, such as the basal layer of the epithelium. In the developing limb bud, the expression of HMGN1 is complementary to Sox9, a master regulator of the chondrocyte lineage. In limb bud micromass cultures, which faithfully mimic in vivo chondrogenic differentiation, loss of HMGN1 accelerates differentiation. Expression of wild-type HMGN1, but not of a mutant HMGN1 that does not bind to chromatin, in Hmgn1-/- micromass cultures inhibits Sox9 expression and retards differentiation. Chromatin immunoprecipitation analysis reveals that HMGN1 binds to Sox9 chromatin in cells that are poised to express Sox9. Loss of HMGN1 elevates the amount of HMGN2 bound to Sox9, suggesting functional redundancy among these proteins. These findings suggest a role for HMGN1 in chromatin remodeling during embryogenesis and in the activation of Sox9 during chondrogenesis.

The Volume of Subscapularis Muscle Remains Unaffected by Supraspinatus Tendon Tears: Three-dimensionally Reconstructed Magnetic Resonance Imaging Analysis.

BACKGROUND: This study aimed to compare the subscapularis muscle volume between the intact groups (group I) and supraspinatus tendon tear groups (group T) based on the sex and three different age groups. METHODS: Subjects with a group I and subjects with group T without any other lesions were retrospectively evaluated from among patients who received a magnetic resonance imaging (MRI) scan between January 2011 and December 2013. The MRI scans were studied by a consultant radiologist. The subscapularis muscle volume was compared according to the age and sex; the age groups were categorized as patients in their 40s, 50s, and 60s. The volume of subscapularis muscle was measured by three-dimensional reconstructed images acquired through the axial section of 1.5T MRI. RESULTS: No statistically significant differences were observed between subscapularis muscle volume of the group I and group T, except for male patients in their 50s (group I: 100,650 mm3 vs. group T: 106,488 mm3) and 60s (group I: 76,347 mm3 vs. group T: 99,549 mm3) (p<0.05). Males had a larger mean volume of subscapularis muscle than females, and the subscapularis muscle volume decreased in a linear manner with increasing age. CONCLUSIONS: Decrease in subscapularis muscle volume was observed with increasing age, and the impact of supraspinatus tear on subscapularis muscle volume is age and sex dependent.

Radiological indicator of reduction adequacy during ankle syndesmosis surgery: A computational cadaveric study.

PURPOSE: We introduced the intraoperative radiological indicator to assess the reduction adequacy without additional procedure or instrument, and propose the optimal syndesmotic screw trajectory. METHODS: Thirty adult cadavers (15 males and 15 females) without ankle problems were enrolled and subjected to continuous 0.75 mm-slice computed tomography (CT) scans. CT images were imported into Mimics® software to reconstruct three-dimensional (3D) model of ankle. Using free 360° rotations with magnification, the 3D mutual relationships of ankle syndesmosis were assessed, and the fibular congruency of incisura was evaluated to determine the optimal screw trajectory. By reformatting the CT scanning plane along the screw direction, the coronal relation of ankle syndesmosis was evaluated to verify the distance between the adjacent bones. RESULTS: The fibula was placed in the concentric position of fibular incisura in the 20 models (concentric group) and 40 models, in an eccentric position (eccentric group). Despite this variant, all fibulas were changed into the concentric position in the proximal part of syndesmotic footprint, which might be the ideal height for syndesmotic screw in our study. The fibular bisecting screw trajectory associated with the ideal height of screw was parallel to the ground if the tibial tubercle was directed to the superior and nearly vertical to the ground floor (TT view). Through the reformatted scanning plane parallel to the screw, the lateral border of talus was always placed more medial than the lateral border of distal tibia in the coronal image. All models had a perfectly equidistant and parallel joint space except the medial aspect. CONCLUSION: The lateral border of talus in the TT view was intraoperatively used as the radiological indicator for ankle syndesmosis widening because it was always placed more medial than the lateral border of distal tibia. The optimal syndesmotic screw trajectory was placed around the proximal syndesmotic footprint and parallel to the ground via the TT view.

Three-dimensional Capsular Volume Measurements in Multidirectional Shoulder Instability.

BACKGROUND: In a previous study undertaken to quantify capsular volume in rotator cuff interval or axillary pouch, significant differences were found between controls and patients with instability. However, the results obtained were derived from two-dimensional cross sectional areas. In our study, we sought correlation between three-dimensional (3D) capsular volumes, as measured by magnetic resonance arthrography (MRA), and multidirectional instability (MDI) of the shoulder. METHODS: The MRAs of 21 patients with MDI of the shoulder and 16 control cases with no instability were retrospectively reviewed. Capsular areas determined by MRA were translated into 3D volumes using 3D software Mimics ver. 16 (Materilise, Leuven, Belgium), and glenoid surface area was measured in axial and coronal MRA views. Then, the ratio between capsular volume and glenoid surface area was calculated, and evaluated with control group. RESULTS: The ratio between 3D capsular volume and glenoid surface area was significantly increased in the MDI group (3.59 ± 0.83 cm3/cm2) compared to the control group (2.53 ± 0.62 cm3/cm2) (p<0.01). CONCLUSIONS: From these results, we could support that capsular volume enlargement play an important role in MDI of the shoulder using volume measurement.

Repressive effects of red bean, Phaseolus angularis, extracts on obesity of mouse induced with high-fat diet via downregulation of adipocyte differentiation and modulating lipid metabolism.

Obesity is generally caused by quantitative changes in adipocyte differentiation and fat metabolism. Only a few studies have been determined the effect of red beans extract on obesity and plasma cholesterol concentration. We have been studied the functional activities of red-bean extracts including anti-oxidative effect against DNA and cell damages. Histological study including micro CT analysis showed that the accumulation of fat in hepatocytes and intestines was significantly decreased in red bean extract treated group. In addition, plasma cholesterol and triglyceride levels were decreased in blood samples. In addition, it was confirmed that the red bean extract inhibited the expression of PPARγ, Fabp4 and RETN genes, which regulate total adipocyte differentiation and lipid metabolism. Red bean extract inhibits the expressions of transcription factors associated with adipocyte differentiation in a dose-dependent manner, thereby inhibiting fat accumulation and decreasing blood lipid levels in obese mice induced by high fat diet.

Mitotic phosphorylation of chromosomal protein HMGN1 inhibits nuclear import and promotes interaction with 14.3.3 proteins.

Progression through mitosis is associated with reversible phosphorylation of many nuclear proteins including that of the high-mobility group N (HMGN) nucleosomal binding protein family. Here we use immunofluorescence and in vitro nuclear import studies to demonstrate that mitotic phosphorylation of the nucleosomal binding domain (NBD) of the HMGN1 protein prevents its reentry into the newly formed nucleus in late telophase. By microinjecting wild-type and mutant proteins into the cytoplasm of HeLa cells and expressing these proteins in HmgN1(-/-) cells, we demonstrate that the inability to enter the nucleus is a consequence of phosphorylation and is not due to the presence of negative charges. Using affinity chromatography with recombinant proteins and nuclear extracts prepared from logarithmically growing or mitotically arrested cells, we demonstrate that phosphorylation of the NBD of HMGN1 promotes interaction with specific 14.3.3 isotypes. We conclude that mitotic phosphorylation of HMGN1 protein promotes interaction with 14.3.3 proteins and suggest that this interaction impedes the reentry of the proteins into the nucleus during telophase. Taken together with the results of previous studies, our results suggest a dual role for mitotic phosphorylation of HMGN1: abolishment of chromatin binding and inhibition of nuclear import.

Increased tumorigenicity and sensitivity to ionizing radiation upon loss of chromosomal protein HMGN1.

We report that loss of HMGN1, a nucleosome-binding protein that alters the compaction of the chromatin fiber, increases the cellular sensitivity to ionizing radiation and the tumor burden of mice. The mortality and tumor burden of ionizing radiation-treated Hmgn1-/- mice is higher than that of their Hmgn1+/+ littermates. Hmgn1-/- fibroblasts have an altered G2-M checkpoint activation and are hypersensitive to ionizing radiation. The ionizing radiation hypersensitivity and the aberrant G2-M checkpoint activation of Hmgn1-/- fibroblasts can be reverted by transfections with plasmids expressing wild-type HMGN1, but not with plasmids expressing mutant HMGN proteins that do not bind to chromatin. Transformed Hmgn1-/- fibroblasts grow in soft agar and produce tumors in nude mice with a significantly higher efficiency than Hmgn1+/+ fibroblasts, suggesting that loss of HMGN1 protein disrupts cellular events controlling proliferation and growth. Hmgn1-/- mice have a higher incidence of multiple malignant tumors and metastases than their Hmgn1+/+ littermates. We suggest that HMGN1 optimizes the cellular response to ionizing radiation and to other tumorigenic events; therefore, loss of this protein increases the tumor burden in mice.

Molecular and cytological features of the mouse B-cell lymphoma line iMycEmu-1.

BACKGROUND: Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMycEmu mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings. We have recently shown that gene-targeted iMycEmu mice that carry a His6-tagged mouse Myc cDNA, MycHis, just 5' of the immunoglobulin heavy-chain enhancer, Emu, are prone to B cell and plasma cell tumors. The predominant tumor (approximately 50%) that arose in the iMycEmu mice on the mixed genetic background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of this study was to establish and characterize a cell line, designated iMycEmu-1, for the in-depth evaluation of LBL in vitro. METHODS: The morphological features and the surface marker expression profile of the iMycEmu-1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMycEmu-1 cells was assessed by spectral karyotyping (SKY). The expression of the inserted MycHis gene was determined using RT-PCR and qPCR. Clonotypic immunoglobulin gene arrangements were detected by Southern blotting. The global gene expression program of the iMycEmu-1 cells and the expression of 768 "pathway" genes were determined with the help of the Mouse Lymphochip(c) and Superarray(c) cDNA micro- and macroarrays, respectively. Array results were verified, in part, by RT-PCR and qPCR. RESULTS: Consistent with their derivation from LBL, the iMycEmu-1 cells were found to be neoplastic IgMhighIgDlow lymphoblasts that expressed typical B-cell surface markers including CD40, CD54 (ICAM-1), CD80 (B7-1) and CD86 (B7-2). The iMycEmu-1 cells harbored a reciprocal T(9;11) and three non-reciprocal chromosomal translocations, over-expressed MycHis at the expense of normal Myc, and exhibited gene expression changes on Mouse Lymphochip microarrays that were consistent with MycHis-driven B-cell neoplasia. Upon comparison to normal B cells using eight different Superarray cDNA macroarrays, the iMycEmu-1 cells showed the highest number of changes on the NFkappaB array. CONCLUSION: The iMycEmu-1 cells may provide a uniquely useful model system to study the growth and survival requirements of Myc-driven mouse LBL in vitro.

Chromosomal protein HMGN1 modulates the expression of N-cadherin.

HMGN1 is a nuclear protein that binds to nucleosomes and alters the accessibility of regulatory factors to their chromatin targets. To elucidate its biological function and identify specific HMGN1 target genes, we generated Hmgn1-/- mice. DNA microarray analysis of Hmgn1+/+ and Hmgn1-/- embryonic fibroblasts identified N-cadherin as a potential HMGN1 gene target. RT-PCR and western blot analysis confirmed a linkage between HMGN1 expression and N-cadherin levels. In both transformed and primary mouse embryonic fibroblasts (MEFs), HMGN1 acted as negative regulator of N-cadherin expression. Likewise, the N-cadherin levels in early embryos of Hmgn1-/- mice were higher than those of their Hmgn1+/+ littermates. Loss of HMGN1 increased the adhesiveness, motility and aggregation potential of Hmgn1-/- MEFs, a phenotype consistent with increased levels of N-cadherin protein. Re-expression of wild-type HMGN1, but not of the mutant HMGN1 protein that does not bind to chromatin, in Hmgn1-/- MEFs, decreased the levels of N-cadherin and restored the Hmgn1+/+ phenotype. These studies demonstrate a role for HMGN1 in the regulation of specific gene expression. We suggest that in MEFs, and during early mouse development, the interaction of HMGN1 with chromatin down-regulates the expression of N-cadherin.

Yam (Dioscorea batatas) Root and Bark Extracts Stimulate Osteoblast Mineralization by Increasing Ca and P Accumulation and Alkaline Phosphatase Activity.

Yam (Dioscorea batatas) is widely consumed as functional food for health promotion mainly in East Asia countries. We assessed whether yam root (tuber) or bark (peel) extracts stimulated the activity of osteoblasts for osteogenesis. MC3T3-E1 cells (mouse osteoblasts) were treated with yam root extracts (water or methanol) (study I) or bark extracts (water or hexane) (study II) within 0~10 µg/mL during the periods of osteoblast proliferation (5~10 day), matrix maturation (11~15 day) and mineralization (16~20 day) as appropriate. In study I, both yam root water and methanol extracts increased cell proliferation as concentration-dependent manner. Cellular collagen synthesis and alkaline phosphatase (ALP) activity, both the indicators of bone matrix protein and inorganic phosphate production for calcification respectively, were also increased by yam root water and methanol extract. Osteoblast calcification as cell matrix Ca and P accumulation was also increased by the addition of yam root extracts. In study II, yam bark extracts (water and hexane) increased osteoblast proliferation and differentiation, as collagen synthesis and ALP activity and osteoblast matrix Ca and P deposition. The study results suggested that both yam root and bark extracts stimulate osteogenic function in osteoblasts by stimulating bone matrix maturation by increasing collagen synthesis, ALP activity, and matrix mineralization.