Expression of epithelial-mesenchymal transition-associated proteins and proliferating cell nuclear antigen in dihydropyridine-induced gingival overgrowth fibroblasts: A preliminary study.

Background/purpose: The clinical features of dihydropyridine-induced gingival overgrowth (DIGO), including extracellular matrix accumulation and cell hyperplasia, are regulated by inflammatory factors (e.g., Interleukin-1ß [IL-1ß]) in combination with calcium channel blockers (e.g., nifedipine [Nif]). We speculated that IL-1ß and Nif (IL-1ß/Nif) may be the main factor modulating the proliferative potential and turnover of fibroblasts in DIGO. Materials and methods: We cultured four DIGO fibroblast strains and analysed the possible effects of IL-1ß/Nif treatments on epithelial-mesenchymal transition (EMT)-associated proteins. We developed short hairpin ribonucleic acids (shRNAs) and used them to explore the role of IL-1ß/Nif in regulating proliferating cell nuclear antigen (PCNA) levels in DIGO tissues. Results: Our results revealed that compared with control cells, DIGO cells stimulated with IL-1ß/Nif had higher levels of the EMT-associated proteins Snail, Slug, and Twist. Moreover, both drugs enhanced androgen receptor (AR), Slug, and PCNA expression. Conclusion: Taken together, our data indicate that proinflammatory cytokines in combination with calcium channel blockers can regulate the expression of EMT-associated proteins and increase the proliferative potential of DIGO fibroblasts.

Analysis of Melt Front Behavior of a Light Guiding Plate during the Filling Phase of Micro-Injection Molding.

When the size of a liquid crystal display (LCD) increases, the light guiding plate (LGP) as the main part of the LCD must adopt a wedge-shaped plate to reduce its weight (the thickness of the LGP decreases because of this) and guide the light to the LCD screen. Micro-injection molding (MIM) is commonly used to manufacture LGPs. During the filling phase of MIM, the entire entering polymer melt front of the LGP should reach the end of the mold cavity at the same time. In this way, there will be no shrinkage or warpage of the LGP in its subsequent application, but it is difficult for the wedge-shaped LGP to meet these requirements. Therefore, the authors hoped to investigate MIM process parameters to change this situation. Otherwise, the LGP is easily deformed during the manufacturing process. Flow characteristics of LGPs were investigated during the filling phase of MIM in this study. Experimental and 3D numerical simulations were used to analyze the hysteresis, i.e., the advance of the polymer melt front of the LGP in MIM. Study results showed that a low injection speed caused a hysteresis effect of the plastic melt front, the solution was to increase the injection speed to improve the situation and an injection speed of 10 cm/s could achieve uniformity of the melt front in MIM. The research results showed that the filling situation of the LGP of MIM in the experiment was very close to that of the 3D numerical simulation.

Clinical Benefits of Minimally Invasive Non-Surgical Periodontal Therapy as an Alternative of Conventional Non-Surgical Periodontal Therapy-A Pilot Study.

Minimally invasive procedures were introduced in periodontics, which could enhance clinical outcomes and reduce post-operative discomfort. However, minimally invasive non-surgical periodontal therapy (MINST) as an alternative modality of conventional non-surgical root surface debridement has not been clearly evaluated by randomized controlled clinical trial. The present study aimed to investigate clinical outcomes and patients' comfort feedback of MINST compared to conventional non-surgical periodontal therapy (CNST). Patients with moderate to severe periodontitis were included. Nine out of ten patients were recruited and completed the post-treatment re-evaluation in this study. Randomized split-mouth design, CNST and MINST on each side, was performed. Clinical parameters, including periodontal probing depth (PD), gingival recession (REC), clinical attachment level (CAL), and gingival bleeding on probing (BOP), were recorded on baseline, 1 month and 3 months post-treatment. Non-parametric statistics were used for analysis. PD, REC, CAL, and BOP were improved after treatment in both CNST and MINST groups. Comfort feedback and gingival recession showed better outcomes in the MINST group than in the CNST group. No statistical significance of parameters was found between CNST and MINST. Within the limitations, minimally invasive non-surgical periodontal therapy could be an alternative modality of conventional non-surgical periodontal therapy. Further studies are required to establish clinical protocol and evidence of MINST.

Analysis of the Warpage Phenomenon of Micro-Sized Parts with Precision Injection Molding by Experiment, Numerical Simulation, and Grey Theory.

In this study, we determined the effects of design and processing parameters of precision injection molding (PIM) to minimize warpage phenomena of micro-sized parts using various plastics (polyoxymethylene (POM), acrylonitrile-butadiene-styrene (ABS), polypropylene (PP), polyamide (PA), and ABS+ polycarbonate (PC)). We applied a numerical simulation (Moldflow) to determine the runner's balance in multi-cavities of the micro-sized part and simulate the warpage phenomenon of micro-parts with PIM. We used simulation data to fabricate a steel mold by computer numerical control (CNC) machining. In this, we study manufactured a micro-sized part and measured its warpage value using various PIM process parameters (melt temperature, mold temperature, injection pressure, and filling time). In order to obtain optimal results (i.e., minimum warpage), we employed the Taguchi method and grey theory to discern the influence of each process parameter on PIM. Finally, we determined that the most significant PIM process parameter influencing the warpage phenomenon of micro-sized parts was the mold temperature, regardless of whether in terms of the experimental results, numerical simulations, or grey theory. The PA material had the most suitable properties for application for micro-sized parts, regardless of whether in terms of experimental results, numerical simulations, or grey theory for PIM. This study also illustrates that micro-sized parts can be fabricated by PIM without the use of micro-injection molding, and we determined that the mold temperature required for molding does not need to be higher than the glass-transition temperature of the material.

Optimal Processing Parameters of Transmission Parts of a Flapping-Wing Micro-Aerial Vehicle Using Precision Injection Molding.

In this study, we designed and fabricated transmission parts for a flapping-wing micro-aerial vehicle (FW-MAV), which was fabricated by precision injection molding, and analyzed its warpage phenomena. First, a numerical simulation (Moldflow) was used to analyze the runner balance and temperature, pressure, and stress distributions of the base, gears, and linkage of the transmission structures in an FW-MAV. These data were then applied to fabricate a steel mold for an FW-MAV. Various process parameters (i.e., injection temperature, mold temperature, injection pressure, and packing time) for manufacturing transmission parts for the FW-MAV by precision injection molding were compared. The Taguchi method was employed to determine causes of warpage in the transmission parts. The experimental results revealed that the causes of warpage in the transmission parts were, in order of importance, the mold temperature, injection pressure, packing time, and injection temperature. After the transmission parts were assembled on the FW-MAV, experiments revealed that the MAV could achieve a flight time of 180 s. Mass production of the FW-MAV by precision injection molding could potentially produce substantial savings in time, manpower, and cost.

Effects of Periodontal Treatment in Patients with Periodontitis and Kidney Failure: A Pilot Study.

Periodontitis and chronic kidney disease are both chronic inflammatory diseases and share some common risk factors. This 3-month pilot study aimed to clarify whether non-surgical periodontal therapy is beneficial in clinical, biochemical, and microbiological conditions in patients with periodontitis and kidney failure. Kidney failure patients with moderate to severe periodontitis were recruited from two hospitals. Treatment group received non-surgical periodontal therapy, and control group received oral hygiene instruction only. Outcome assessments were conducted 1 and 3 months after treatment. Non-parametric tests were used to analyze the patient-level data. Periodontal site-level assessments were analyzed by Student t-test and paired t-test. Statistical significance was set at p-value < 0.05. A total of 11 subjects completed the study. There was no significant difference between groups in all-cause mortality, cardiovascular events, infection events, systemic parameters, and serum biomarkers. Comparing to control group, clinical periodontal parameters, gingival crevicular fluid interleukin-1ß (IL-1ß) level and periodontal pathogens showed significant improvement in the treatment group. Non-surgical periodontal treatment did not change systemic outcomes in kidney failure patients, but changed the local micro-environment.

An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability.

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.

Optimized Micro-Pattern Design and Fabrication of a Light Guide Plate Using Micro-Injection Molding.

This study examined the uniformity of illuminance field distributions of light guide plates (LGPs). First, the authors designed microstructural patterns on the surface of an LGP. Then, a mold of the LGP with the optimal microstructural design was fabricated by a photolithography method. Micro-injection molding (µIM) was used to manufacture the molded LGPs. µIM technology can simultaneously manufacture large-sized wedge-shaped LGPs and micro-scale microstructures. Finally, illuminance values of the field distributions of the LGPs with various microstructures were obtained through optical field measurements. This study compared the illuminance field distributions of LGPs with various designs and structures, which included LGPs without and those with microstructure on the primary design and the optimal design. The average illuminance of the LGP with microstructures and the optimal design was roughly 196.1 cd/m2. Its average illuminance was 1.3 times that of the LGP without microstructures. This study also discusses illuminance field distributions of LGPs with microstructures that were influenced by various µIM process parameters. The mold temperature was found to be the most important processing parameter affecting the illuminance field distribution of molded LGPs fabricated by µIM. The molded LGP with microstructures and the optimal design had better uniformity than that with microstructures and the primary design and that without microstructures. The uniformity of the LGP with microstructures and the optimal design was roughly 86.4%. Its uniformity was nearly 1.65 times that of the LGP without microstructures. The optimized design and fabrication of LGPs with microstructure exhibited good uniformity of illuminance field distributions.

Color Stability and Staining Susceptibility of Direct Resin-Based Composites after Light-Activated In-Office Bleaching.

This study evaluated color stability and staining susceptibility of five direct resin-based composites (RBCs) subjected to light-activated in-office bleaching with 40% hydrogen peroxide (HP). The test materials included 5 RBCs, which consisted of one nano-filled, one sub-micron, one bulk-filled, and two nano-hybrid RBC types. Ten disc-shaped specimens of each RBC were fabricated and divided into bleaching (BLE) and non-bleaching (CON) groups (n = 5 for each group). Specimens were then immersed in red wine solution over 4 h. A spectrophotometer was used to obtain Commission Internationale de l'Eclairage (CIE) L*a*b* parameters for each of the following periods tested: before bleaching (TBA), after bleaching (TBL), and after staining (TST). Color stability and staining susceptibility were evaluated using two metrics, CIEDE2000 color differences (ΔE00) and whiteness variations using the whiteness index (ΔWID). Data were analyzed using repeated measures two-way analysis of variance (ANOVA) (α = 0.05). Statistically significant and clinically unaccepted ΔE00 and ΔWID were observed for all tested specimens between TBA and TBL. The nano-hybrid type RBCs showed the highest discoloration among materials after bleaching treatment. The BLE group exhibited significantly higher ΔE00 and ΔWID than the CON group for all the tested RBCs between TBA and TST. The sub-micron type RBC showed the highest discoloration among materials after immersion in the red wine. Conclusion. The light-activated in-office bleaching with 40% HP's influences on color and whiteness index were material-dependent. The use of bleaching treatment also increased the susceptibility to red wine for all RBCs.

Bioactivity and Bone Cell Formation with Poly-ε-Caprolactone/Bioceramic 3D Porous Scaffolds.

This study applied poly-ε-caprolactone (PCL), a biomedical ceramic powder as an additive (nano-hydroxyapatite (nHA) or ß-tricalcium diphosphate (ß-TCP)), and sodium chloride (NaCl) and ammonium bicarbonate ((NH4)HCO3) as porogens; these stuffs were used as scaffold materials. An improved solvent-casting/particulate-leaching method was utilized to fabricate 3D porous scaffolds. In this study we examined the physical properties (elastic modulus, porosity, and contact angle) and degradation properties (weight loss and pH value) of the 3D porous scaffolds. Both nHA and ß-TCP improved the mechanical properties (elastic modulus) of the 3D porous scaffolds. The elastic modulus (0.15~1.865 GPa) of the various composite scaffolds matched that of human cancellous bone (0.1~4.5 GPa). Osteoblast-like (MG63) cells were cultured, a microculture tetrazolium test (MTT) was conducted and alkaline phosphatase (ALP) activity of the 3D porous scaffolds was determined. Experimental results indicated that both nHA and ß-TCP powder improved the hydrophilic properties of the scaffolds. The degradation rate of the scaffolds was accelerated by adding nHA or ß-TCP. The MTT and ALP activity tests indicated that the scaffolds with a high ratio of nHA or ß-TCP had excellent properties of in vitro biocompatibility (cell attachment and proliferation).

Role of IL-6 and STAT3 signaling in dihydropyridine-induced gingival overgrowth fibroblasts.

OBJECTIVES: This study analyzed the role of the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) pathway in dihydropyridine-induced gingival overgrowth (DIGO) fibroblasts. MATERIALS AND METHODS: Tissue samples were obtained through surgical dissection from five DIGO patients and five healthy individuals. Cell cultures were conditioned with nifedipine (Nif) (0.34 µM) and stimulated with IL-1ß (10 ng/ml) to clarify whether IL-6 upregulates extracellular matrix overproduction or has an impact on the cell proliferation rate of DIGO fibroblasts. STAT3 was knocked down using short hairpin (sh)RNA to determine its role in collagen (Col) type I alpha 1 (Colα1(I)) synthesis. RESULTS: Results showed that phosphorylated (p)STAT3 nuclear translocation was activated by a simulated autocrine concentration (50 ng/ml) of IL-6, and application of an anti-IL-6 antibody significantly decreased the pSTAT3/STAT3 ratio in DIGO fibroblasts. STAT3 knockdown significantly decreased STAT3 and Colα1(I) expressions in DIGO cells. DIGO tissues presented stronger proliferating cell nuclear antigen (PCNA) expression than did healthy individuals under the effect of IL-1ß/Nif treatment. CONCLUSIONS: Gingival inflammation (e.g., IL-1ß) and taking dihydropyridine (e.g., Nif) may additively stimulate Col overproduction through the IL-6-STAT3-Colα1(I) cascade in DIGO cells. IL-6-STAT3 signaling may be considered a target for the control of DIGO.

Analysis of clinical associated factors of vertical root fracture cases found in endodontic surgery.

BACKGROUND/PURPOSE: Early diagnosis of vertical root fracture (VRF) has been a great challenge. Since there is no single specific etiology identified, prevention of VRFs in endodontically treated teeth is quite difficult. The study aimed to evaluate the clinical associated factors of VRFs. MATERIALS AND METHODS: A retrospective observational study of medical charts was conducted in the Department of Endodontics of Taipei Medical University Hospital in Taiwan from January 2012 to July 2018. Logistic regression model was performed to determine the association between VRF and its clinical associated factors, inclusive of the tooth characteristics (age, gender and tooth type) and iatrogenic risk factors (history of root canal treatment, restoration and post). RESULTS: A total of 359 teeth were included in the study. The prevalence of VRF on a tooth basis was 18.7%. The result showed that age of more than 50 years (adjusted OR = 3.20, 95% CI: 1.81-5.64, p < 0.001) had significant higher risk of VRFs than those of less than 50 years. The subjects of molars (adjusted OR = 4.31; 95%CI = 2.24-8.27; P value < 0.001) and premolars (adjusted OR = 2.61; 95%CI = 1.16-5.86; P value = 0.021) had significant higher risk of VRFs than those of incisors. However, other variables such as gender, history of root canal treatment, restoration and post had no significant association with the VRF. CONCLUSION: Age and tooth type are significant clinical associated factors of VRF. In the presence of these factors as well as predominant diagnostic factors, clinical practitioners should be aware of the possible diagnosis of VRFs.

Fully Digital Workflow for Planning Static Guided Implant Surgery: A Prospective Accuracy Study.

The accuracy of static guided implant surgery (sGIS) using conventional planning workflow has been extensively examined; however, more information is required to justify the application of fully digital planning protocol. The purpose of this study was to investigate the clinical accuracy of sGIS with a fully digital planning workflow. Twenty-one partially edentulous patients were enrolled in this prospective study. Cone-beam computed tomography (CBCT) and intraoral scans were taken and superimposed by matching the dental surface images directly (surface registration protocol) or by matching fiducial markers on a stereolithographic (SLA) radiographic template fabricated from the digital data of the intraoral scan (fiducial marker registration protocol). Virtual implant treatment plans were then determined, and tooth-supported SLA surgical guides were fabricated according to the plans. Twenty-six implant surgeries were performed via the surgical guide by one surgeon. Pre- and post-operative CBCT images were superimposed, and the positional and angular deviations between placed and planned implants were measured with metrology software. A total of 43 fully guided implants were placed, in which 25 implants were planned with the surface registration protocol. Implants planned based on the surface registration protocol had a larger mean angular deviation than the fiducial marker registration protocol. No significant differences were found for any deviations of the examined variables. Within the limits of this study, we concluded that the clinical accuracy of the sGIS planned with a fully digital workflow was consistent with the conventional workflow for partially edentulous patients.

Therapeutic potential of proteasome inhibitors for dihydropyridine-induced gingival overgrowth.

OBJECTIVES: NF-κB plays a crucial role in collagen overproduction in dihydropyridine-induced gingival overgrowth (DIGO) fibroblasts. We aim to investigate the role of the kappa B (IκB) kinase (IKK)-NF-κB pathway and downstream collagen type I (Col I) synthesis in DIGO cells and to demonstrate the therapeutic strategy of interference of this pathway with proteasome inhibitors. METHODS: Gingival fibroblasts from DIGO (n = 5) and healthy (n = 5) patients were selected and stimulated with IL-1ß, nifedipine, or both. All experiments were run in triplicate and independently for each primary cell sample. RESULTS: The results demonstrated that both drugs additively mediated NF-κB activity by activating IKKα/ß phosphorylation. They also triggered nuclear translocation of NF-κB, Rela, and p50 (*p < .05) and increased Col I production in both healthy and DIGO cells. The addition of proteasome inhibitors, including bortezomib and MG132, promoted the accumulation of phosphorylated p-IκBα, prevented the subsequent cytosol-to-nuclear translocation of p50 and Rela (*p < .05), and abbreviated the biosynthesis of Col I in DIGO cells. CONCLUSIONS: We suggested that IKK-IκBα activation is mediated by proinflammatory cytokines and CCBs in DIGO cells and triggers downstream NF-κB-Col I synthesis. Proteasome inhibitors may strategically interfere with the IKK-IκBα-NF-κB-Col I pathway and inhibit the etiopathogenesis of DIGO.

The association between clinical diagnostic factors and the prevalence of vertical root fracture in endodontic surgery.

BACKGROUND/PURPOSE: Diagnosis of vertical root fractures (VRFs) can often be challenging due to the similarity of signs and symptoms with other common dental infectious diseases. This study was aimed at evaluating the potential relationship between VRFs and commonly used clinical diagnostic factors. METHODS: 330 root-filled teeth with endodontic failures were subjected to endodontic microsurgery over a six-year period. VRFs were identified in 61 teeth. A randomly age- and sex-matched retrospective case-control study was conducted on a subset of 59 root-filled teeth with VRFs (cases) and 177 root-filled teeth without VRFs (controls). The strength of association between preoperative signs and radiographic findings and VRFs was evaluated using logistic regression model. RESULTS: Sinus tract, periodontal pocket depth ≥5 mm, periodontal swelling or abscess, and radiological image of J-shaped or "halo" radiolucency were significantly more frequent in cases than in controls (p < 0.05). With regard to logistic regression analysis, J-shaped or "halo" radiolucency demonstrated the greatest association with VRF, followed by periodontal pocket depth ≥5 mm, sinus tract, and periodontal swelling or abscess. Approximately 70% of cases manifested themselves as combinations of at least two of these factors. Teeth having two and three or four of these factors had 3.14 times and 11.64 times higher risks for the presentations of VRFs, respectively (p < 0.001). CONCLUSION: The major risk for VRFs was represented by those presenting radiological image of J-shaped or "halo" radiolucency, periodontal pocket depth ≥5 mm, sinus tract, and periodontal swelling or abscess simultaneously.

Hybrid micro/nanostructural surface offering improved stress distribution and enhanced osseointegration properties of the biomedical titanium implant.

OBJECTIVES: The aim of the present study was to investigate the surface characteristic, biomechanical behavior, hemocompatibility, bone tissue response and osseointegration of the optimal micro-arc oxidation surface-treated titanium (MST-Ti) dental implant. MATERIALS AND METHODS: The surface characteristic, biomechanical behavior and hemocompatibility of the MST-Ti dental implant were performed using scanning electron microscope, finite element method, blood dripping and immersion tests. The mini-pig model was utilized to evaluate the bone tissue response and osseointegration of the MST-Ti dental implant in vivo. Data were analyzed by analysis of variance using the Student's t-test (P ≤ 0.05). RESULTS: The hybrid volcano-like micro/nanoporous structure was formed on the surface of the MST-Ti dental implant. The hybrid volcano-like micro/nanoporous surface played an important role to improve the stress transfer between fixture, cortical bone and cancellous bone for the MST-Ti dental implant. Moreover, the MST-Ti implant was considered to have the outstanding hemocompatibility. In vivo testing results showed that the bone-to-implant contact (BIC) ratio significantly altered as the implant with micro/nanoporous surface. After 12 weeks of implantation, the MST-Ti dental implant group exhibited significantly higher BIC ratio than the untreated dental implant group. In addition, the MST-Ti dental implant group also presented an enhancing osseointegration, particularly in the early stages of bone healing. CONCLUSION: It can be concluded that the micro-arc oxidation approach induced the formation of micro/nanoporous surface is a promising and reliable alternative surface modification for Ti dental implant applications.

Influence of Deformation and Stress between Bone and Implant from Various Bite Forces by Numerical Simulation Analysis.

Endosseous oral implant is applied for orthodontic anchorage in subjects with multiple tooth agenesis. Its effectiveness under orthodontic loading has been demonstrated clinically and experimentally. This study investigates the deformation and stress on the bone and implant for different bite forces by three-dimensional (3D) finite element (FE) methods. A numerical simulation of deformation and stress distributions around implants was used to estimate the survival life for implants. The model was applied to determine the pattern and distribution of deformations and stresses within the endosseous implant and on supporting tissues when the endosseous implant is used for orthodontic anchorage. A threaded implant was placed in an edentulous segment of a human mandible with cortical and cancellous bone. Analytical results demonstrate that maximum stresses were always located around the implant neck in marginal bone. The results also reveal that the stress for oblique force has the maximum value followed by the horizontal force; the vertical force causes the stress to have the minimum value between implant and bone. Thus, this area should be preserved clinically to maintain the structure and function of a bone implant.

Corrigendum to "Osteoporosis Recovery by Antrodia camphorata Alcohol Extracts through Bone Regeneration in SAMP8 Mice".

[This corrects the article DOI: 10.1155/2016/2617868.].

Functional Recovery in Osteoarthritic Chondrocytes Through Hyaluronic Acid and Platelet-Rich Plasma-Inhibited Infrapatellar Fat Pad Adipocytes.

BACKGROUND: Recent studies have shown evidence that higher adiposity in the infrapatellar fat pad (IFP) induces inflammatory phenotypes in the knee joint and thereby contributes to the development and progression of osteoarthritis (OA). In particular, IFP adipocyte-derived inflammatory cytokines participate in pathological events. Our previous research has already addressed the therapeutic efficacy of hyaluronic acid and platelet-rich plasma (HA+PRP), including the promotion of cartilage regeneration and the inhibition of inflammation. The current study aimed to explore the remedial action of coadministered HA+PRP in OA recovery via IFP adipocyte inhibition. HYPOTHESIS: HA+PRP repairs OA articular cartilage by inhibiting the release of adipokines from IFP adipocytes. STUDY DESIGN: Controlled laboratory study. METHODS: IFP adipocytes and articular chondrocytes were obtained from 10 patients with OA, and the effects of releasates containing cytokines and adipokines in IFP adipocyte-derived conditioned medium (IACM) on articular chondrocytes and IFP adipocytes themselves were evaluated. The therapeutic efficacy of exogenous HA+PRP was determined through its administration to cocultured IFP adipocytes and articular chondrocytes and further demonstrated in a 3-dimensional (3D) arthritic neocartilage model. RESULTS: The IACM and IFP adipocyte-induced microenvironment could induce dedifferentiated and inflammatory phenotypes in articular chondrocytes. HA+PRP decreased the inflammatory potential of IFP adipocytes through the profound inhibition of cytokines and adipokines. The IACM-mediated and -reduced cartilaginous extracellular matrix could also be recovered through HA+PRP in the 3D arthritic neocartilage model. CONCLUSION: IFP adipocyte-derived releasates mediated inflammatory response dedifferentiation in chondrocytes, which was recovered through HA+PRP administration. CLINICAL RELEVANCE: Our findings demonstrated that HA+PRP effectively diminished IFP adipocyte-promoted inflammation in articular chondrocytes, indicating that the IFP could be a potential therapeutic target for OA therapy.

Osteoporosis Recovery by Antrodia camphorata Alcohol Extracts through Bone Regeneration in SAMP8 Mice.

Antrodia camphorata has previously demonstrated the efficacy in treating cancer and anti-inflammation. In this study, we are the first to evaluate Antrodia camphorata alcohol extract (ACAE) for osteoporosis recovery in vitro with preosteoblast cells (MC3T3-E1) and in vivo with an osteoporosis mouse model established in our previous studies, ovariectomized senescence accelerated mice (OVX-SAMP8). Our results demonstrated that ACAE treatment was slightly cytotoxic to preosteoblast at 25 µg/mL, by which the osteogenic gene expression (RUNX2, OPN, and OCN) was significantly upregulated with an increased ratio of OPG to RANKL, indicating maintenance of the bone matrix through inhibition of osteoclastic pathway. Additionally, evaluation by Alizarin Red S staining showed increased mineralization in ACAE-treated preosteoblasts. For in vivo study, our results indicated that ACAE inhibits bone loss and significantly increases percentage bone volume, trabecular bone number, and bone mineral density in OVX-SAMP8 mice treated with ACAE. Collectively, in vitro and in vivo results showed that ACAE could promote osteogenesis and prevent bone loss and should be considered an evidence-based complementary and alternative medicine for osteoporosis therapy through the maintenance of bone health.