A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10-7-7.31 × 10-6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10-7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10-6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

Alterative effects of an oral alginate extract on experimental rabbit osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly. However, few agents with high efficacy and low side effects have been developed to treat OA. In this study, we evaluated the effects of the alginate extract named CTX in OA cell and rabbit models. RESULTS: CTX was formulated by hydrolyzing sodium alginate polymers with alginate lyase and then mixing with pectin. HPLC was used to analyze the CTX content. Human chondrosarcoma SW1353 cells treated with interleukin-1ß were used as OA model cells to investigate the effects of CTX on chondrocyte inflammation and anabolism. CTX at concentrations up to 1000 µg/ml exerted low cytotoxicity. It inhibited the gene expression of proinflammatory matrix metalloproteinases (MMPs) including MMP1, MMP3 and MMP13 in a dose-dependent manner and increased the mRNA level of aggrecan, the major proteoglycan in articular cartilage, at 1000 µg/ml. Thirteen-week-old New Zealand White rabbits underwent a surgical anterior cruciate ligament transection and were orally treated with normal saline, glucosamine or CTX for up to 7 weeks. Examinations of the rabbit femur and tibia samples demonstrated that the rabbits taking oral CTX at a dosage of 30 mg/kg/day suffered lesser degrees of articular stiffness and histological cartilage damage than the control rabbits. CONCLUSIONS: The gene expression profiles in the cell and the examinations done on the rabbit cartilage suggest that the alginate extract CTX is a pharmaco-therapeutic agent applicable for OA therapy.

Injectable hyaluronic-acid-doxycycline hydrogel therapy in experimental rabbit osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly adults. However, few long-lasting pharmacotherapeutic agents with low side effects have been developed to treat OA. We evaluated the therapeutic effects of intra-articular injections of hydrogels containing hyaluronic acid (HA) and doxycycline (DOX) in a rabbit OA model. RESULTS: Thirteen week old New Zealand White rabbits undergone a partial meniscectomy and unilateral fibular ligament transection were administered with either normal saline (NT), HA, DOX or HA-DOX hydrogels on day 0, 3, 6, 9 and 12; animals were also examined the pain assessment in every three days. The joint samples were taken at day 14 post-surgery for further histopathological evaluation. The degree of pain was significantly attenuated after day 7 post-treatment with both HA and HA-DOX hydrogels. In macroscopic appearance, HA-DOX hydrogel group showed a smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation in compare to HA or DOX treatment alone. In the areas with slight OA changes, HA-DOX hydrogel group exhibited normal distribution of chondrocytes, indicating the existence of cartilage regeneration. In addition, HA-DOX hydrogels also ameliorated the progression of OA by protecting the injury of articular cartilage layer and restoring the elastoviscosity. CONCLUSION: Overall, from both macroscopic and microscopic data of this study indicate the injectable HA-DOX hydrogels presented as a long-lasting pharmacotherapeutic agent to apply for OA therapy.

Cinnamophilin isolated from Cinnamomum philippinense protects against collagen degradation in human chondrocytes.

To investigate the therapeutic potential of naturally occurring cinnamophilin against cartilage degradation and its action mechanisms, its effects on matrix metalloproteinase (MMP)-1 and -13 induction were examined in the human SW1353 chondrocytic cell line. Human chondrocytes (SW1353) were stimulated with interleukin (IL)-1ß, and then mitogen-activated protein kinase (MAPK) and c-Jun activations, inhibitory κB-α (IκB-α) degradation, and MMP-1, and 13 expressions were assayed by a Western blot analysis. Cinnamophilin strongly inhibited MMP-1 and -13 induction in IL-1ß-treated (30 ng/mL) SW1353 cells in a concentration-dependent manner, and it also reduced MAPK family members including extracellular signal-regulated kinase (ERK), p38 MAPKs, and c-Jun N-terminal kinase. Moreover, nuclear factor (NF)-κB signaling activation through IκB-α degradation, IκB kinase (IKK)-α/ß, and p-65 phosphorylation was restored by cinnamophilin upon IL-1ß stimulation. Importantly, results showed that IL-1ß-induced activation of phosphorylated (p)-c-Jun in chondrocytes was significantly inhibited by cinnamophilin. These results indicate that cinnamophilin inhibited MMP-1 and -13 expressions in IL-1ß-treated chondrocytes through either NF-κB or ERK/p38 MAPK downregulation and/or suppressing p-c-Jun pathways. Furthermore, these findings suggest that cinnamophilin may have the potential for chondroprotection against collagen matrix breakdown in cartilage of diseased tissues such as those found in arthritic disorders.

Cinnamic aldehyde, an anti-inflammatory component in Du-Huo-Ji-Sheng-Tang, ameliorates arthritis in II collagenase and monosodium iodoacetate induced osteoarthritis rat models.

Background and aim: Du-Huo-Ji-Sheng-Tang (DHJST) is a Chinese herbal formula used for arthralgia and arthritis treatment clinically. This study aims to evaluate the joint-protecting efficacy of DHJST and to identify the active constituents as the evaluation marker. Experimental procedure: DHJST can be categorized into three recipes: Blood-tonifying-herbs Si-Wu-Tang (SWT), Wind-dampness-dispelling-herbs (WDH) and Qi-tonifying-herbs (TH). All formulas were used to explore the joint-protecting efficacies. Results and conclusion: s: Firstly, DHJST could decrease the arthritis progression in the monosodium-iodoacetate-induced rat and cure arthritis in the type II collagenase-induced rat. Further, in lipopolysaccharide-stimulated RAW 264.7 cells, DHJST, TH and Cinnamomum cassia (CC), an ingredient in TH, were the most potent nitric oxide (NO) and prostaglandin E2 (PGE2) inhibitors. The major components, cinnamic aldehyde, showed the strongest NO and PGE2 inhibition. Up-regulated inducible NO synthase (iNOS) and cyclooxygenase-2 were inhibited by DHJST, TH, CC, and cinnamic aldehyde. In interleukin-1ß-stimulated primary chondrocytes, upregulated iNOS was inhibited by DHJST, TH, Cinnamomum cassia, and cinnamic aldehyde. Upregulated matrix metalloprotease-13 was only inhibited by DHJST and TH and Eucommia ulmoides (EU) extract. Results suggest that DHJST presented joint-protective and cure arthritis effects. TH presented equal joint-protective effects as DHJST. The major anti-inflammatory ingredient in TH was Cinnamomum cassia in TH. And cinnamic aldehyde was the potent anti-inflammatory active compound in Cinnamomum cassia. Therefore, this study may facilitate the modern use of DHJST with TH as a simplified version but equally effective anti-osteoarthritic agents with cinnamic aldehyde as a quality control marker of DHJST and TH in osteoarthritis prevention or treatment.

Is medical students' moral orientation changeable after preclinical medical education?

PURPOSE: Moral orientation can affect ethical decision-making. Very few studies have focused on whether medical education can change the moral orientation of the students. The purpose of the present study was to document the types of moral orientation exhibited by medical students, and to study if their moral orientation was changed after preclinical education. METHODS: From 2007 to 2009, the Mojac scale was used to measure the moral orientation of Taiwan medical students. The students included 271 first-year and 109 third-year students. They were rated as a communitarian, dual, or libertarian group and followed for 2 years to monitor the changes in their Mojac scores. RESULTS: In both first and third-year students, the dual group after 2 years of preclinical medical education did not show any significant change. In the libertarian group, first and third-year students showed a statistically significant increase from a score of 99.4 and 101.3 to 103.0 and 105.7, respectively. In the communitarian group, first and third-year students showed a significant decline from 122.8 and 126.1 to 116.0 and 121.5, respectively. CONCLUSION: During the preclinical medical education years, students with communitarian orientation and libertarian orientation had changed in their moral orientation to become closer to dual orientation. These findings provide valuable hints to medical educators regarding bioethics education and the selection criteria of medical students for admission.

Students' view upon graduation: a survey of medical education in Taiwan.

BACKGROUND: Improving the quality of medical education is a key goal of government policy in Taiwan. The aim of this study was to reflect the responses of medical education from the perspective of graduating medical students in Taiwan. This is the first survey study of medical education in Taiwan. METHODS: Using the Medical School Graduation Questionnaire from the Association of American Medical Colleges (AAMC), we distributed 406 questionnaires to medical students of four medical schools in their last semester, and received 270 back (response rate, 66.5%). There were 11 medical schools in Taiwan. Most questions were assessed on a 5-point Likert scale. RESULTS: Students identified genetics, biochemistry, and ethics as the three most important premedical subjects preparing them for medical education and gross anatomy, physiology, and pharmacology as the three most helpful basic science subjects preparing them for clinical clerkships and electives. Most Taiwanese students were satisfied with their learning experience in internal medicine. Only 55.9% of students were confident that they had acquired the clinical skills required to become a resident, and 70.7% were satisfied with the quality of their medical education. CONCLUSION: The study offers preliminary results on the views of graduating students on the medical education system in Taiwan. In particular, our government and medical educators need to continuously put more effort into building students' confidence in their clinical skills.

Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes.

BACKGROUND: Osteoarthritis (OA) is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood. METHODS: We investigated the effects of the CC chemokine eotaxin-1 (CCL11) on the matrix metalloproteinase (MMP) expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes. RESULTS: Eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK) and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA) inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression is specifically mediated by the G protein-coupled eotaxin-1 receptor activities. Interestingly, little amount of MMP-3 protein was detected in the cell lysates of eotaxin-1-treated SW1353 cells, and most of MMP-3 protein was in the culture media. Furthermore we found that the eotaxin-1-dependent MMP-3 protein secretion was regulated by phospholipase C (PLC)-protein kinase C (PKC) cascade and c-Jun N-terminal kinase (JNK)/mitogen-activated protein (MAP) kinase pathways. These data indicate a specific regulation of MMP-3 secretion also by eotaxin-1 receptor activities. CONCLUSIONS: Eotaxin-1 not only induces MMP-3 gene expression but also promotes MMP-3 protein secretion through G protein-coupled eotaxin-1 receptor activities. Chemokines, such as eotaxin-1, could be a potential candidate in the diagnosis and treatment of arthritis.

Denervation dynamically regulates integrin alpha7 signaling pathways and microscopic structures in rats.

BACKGROUND: Peripheral nerve injury causes serious problems in orthopedic and plastic surgeries. Cell adhesion molecules such as integrin alpha7 provoke cell binding and signaling pathways within myofibers. Expression profiles of integrin alpha7 signaling pathways and the molecule's microscopic structure were assessed to investigate the long-term dynamic changes in denervated rat skeletal muscle. METHODS: A denervated rat skeletal muscle model was established by severing the sciatic nerve for 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 20 weeks, and 26 weeks. Molecular expressions were investigated by mRNA and Western blot. The structural alterations were detected by immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. RESULTS: The denervated muscle atrophy presented the following dynamic molecular alterations: an initial increase around postdenervation in week (PIW) 8 and then a subsequent decay of integrin alpha7, integrin downstream signaling pathway (Ras or Raf or, ERK1/2), Akt, cleaved caspase-3, fast myosin heavy chain (MHC), beta actin, and RhoA. We demonstrated that the expressions of multiple signaling molecules were highly upregulated at PIW 8 (p<0.01). Scanning electron microscopy findings of the surface textures of myofibers showed more severe damage at PIW 8 and subsequently became smoother. Inner structures of myofibers separated with discontinuity on transmission electron microscopy examinations. CONCLUSION: Our novel finding showed that time-series alterations of integrin alpha7 signaling molecules and surface microstructures in the long-term denervated rat skeletal muscle are biphasic and coherently dynamic. Persisted p-Akt elevation suggested that denervated muscle may regenerate if reinnervation or other treatment was performed.

Downregulation of the integrin α(v) signaling pathway in uterine leiomyomas.

OBJECTIVE: To investigate alterations of integrin α(v), survival and apoptosis signaling pathways in uterine leiomyomas. MATERIALS AND METHODS: In a prospective study of 50 women with uterine leiomyomas that had been pathologically confirmed, specimens were obtained laparoscopically from 2007 to 2009. The expressions of integrin α(v) signaling pathways (Ras/Raf/ERK1/2, Akt and cleaved caspase-3), surface microstructures by surface electron microscopy and immunohistochemical findings were assessed. RESULTS: The study yielded novel results: (1) the integrin α(v) expression approached a low level (mRNA 0.39 ± 0.06, protein 0.47 ± 0.08) with coherent alterations of its downstream signaling molecules (Ras, p-c-Raf, p-ERK1/2) (p < 0.001); (2) smoother surface microstructures of uterine leiomyomas were correlated with low integrin α(v) expressions, and (3) survival signaling and apoptosis signaling were significantly down- and upregulated respectively (p < 0.001). CONCLUSION: Integrin α(v) and related survival signaling pathways were downregulated, but the apoptosis was upregulated in uterine leiomyomas. Benign smooth-contoured tumors may have low integrin expressions and cancer invasion potentials.

Primitive results after medial-pivot knee arthroplasties: a minimum 5-year follow-up study.

Paradoxical anterior movement of the femoral condyles after total knee arthroplasty (TKA) often attenuates the extension mechanism and causes a suboptimal outcome. The medial-pivot implant design aimed to confine anterior movement and emulate physiologic knee kinematics. In our study, a consecutive series of 58 medial-pivot TKA were enrolled with a minimum 5-year follow-up. The Knee Society score improved from 30.5 to 91.1 in objective and from 36.7 to 82.3 in functional scale. The average range of motion was 115.4 degrees . The medial-pivot TKA provided significant improvement in the postoperative range of motion, objective Knee Society score, pain scale, and functional score (P < .05) statistically. A larger sample and longer follow-up are recommended to draw definitive conclusions of this new implant design.

Correlation between scoliosis and breast asymmetries in women undergoing augmentation mammaplasty.

BACKGROUND: Breast asymmetries and scoliosis influence the results of augmentation mammaplasty. Although a variety of methods have been proposed to resolve breast asymmetries, to date, no simple preoperative algorithm has been proposed for predicting the breast volume and decreasing breast asymmetries in the place of subjective or expensive evaluation. The relationship between the scoliosis and breast volume asymmetry was further analyzed statistically in this study. METHODS: The study enrolled 60 scoliotic patients from 780 patients undergoing augmentation mammaplasty between January 2000 and March 2008. The average follow-up period was 2 years. The inclusion criteria required hypoplastic breasts, a difference in bilateral breast volumes greater than 20 ml, and scoliosis with a Cobb angle greater than 10 degrees . The authors' surgical algorithm demonstrated an anthropomorphic equation for predicting breast volume and selecting the correct implant size. RESULTS: Pearson regression analysis showed that the breast volume asymmetry difference was significantly correlated with the severity of scoliosis (Cobb angle) (correlation coefficient, 0.901). No correlation between the difference in pre- and postoperative nipple and inframammary levels and the severity of scoliosis was noted. Augmentation mammaplasty significantly decreased the breast asymmetry differences (volume and nipple level) (p < 0.001). The average preoperative estimated breast volume was 45.3 ml for the smaller breast and 88.4 ml for the larger breast. CONCLUSION: This study found that the severity of scoliosis showed significant correlation with the breast volume asymmetry differences. Augmentation mammaplasty for breast asymmetries decreased not only the volume difference but also the difference in nipple levels.

Accurate visual and haptic burring surgery simulation based on a volumetric model.

Burring surgery is mainly implemented for fine or critical structures and widely used in orthopedic, oral and maxillofacial, ENT and neurosurgery departments to delicately cut or polish bones, joints or other tissues. This paper describes a volume manipulation method that extends a voxel with multiple values to represent accurate burred changes on tissue surfaces. Tissue surface reconstruction is implemented for the local burred surface to provide a real-time visual response. A burring force vector for a haptic response is calculated by detecting which parts of a bur contact tissue and summated from tissue removal loads on the contacted parts. A spine surgery example showed that rough surface features by gross cutting or smooth features by fine cutting can be clearly demonstrated and high haptic reality can be achieved by our simulations. The burring surgery simulator with the accurate visual and haptic responses can be an effective rehearsing and training tool.

Runx2-mediated bcl-2 gene expression contributes to nitric oxide protection against hydrogen peroxide-induced osteoblast apoptosis.

Nitric oxide (NO) can regulate osteoblast activities. This study was aimed to evaluate the protective effects of pretreatment with sodium nitroprusside (SNP) as a source of NO on hydrogen peroxide-induced osteoblast insults and its possible mechanisms. Exposure of human osteosarcoma MG63 cells to hydrogen peroxide significantly increased cellular oxidative stress, but decreased ALP activity and cell viability, inducing cell apoptosis. Pretreatment with 0.3 mM SNP significantly lowered hydrogen peroxide-induced cell insults. Treatment of human MG63 cells with hydrogen peroxide inhibited Bcl-2 mRNA and protein production, but pretreatment with 0.3 mM SNP significantly ameliorated such inhibition. Sequentially, hydrogen peroxide decreased the mitochondrial membrane potential, but increased the levels of cytochrome c and caspase-3 activity. Pretreatment with 0.3 mM SNP significantly lowered such alterations. Exposure to hydrogen peroxide decreased Runx2 mRNA and protein syntheses. However, pretreatment with 0.3 mM SNP significantly lowered the suppressive effects. Runx2 knockdown using RNA interference inhibited Bcl-2 mRNA production in human MG63 cells. Protection of pretreatment with 0.3 mM SNP against hydrogen peroxide-induced alterations in ALP activity, caspase-3 activity, apoptotic cells, and cell viability were also alleviated after administration of Runx2 small interference RNA. Thus, this study shows that pretreatment with 0.3 mM SNP can protect human MG63 cells from hydrogen peroxide-induced apoptotic insults possibly via Runx2-involved regulation of bcl-2 gene expression.

Disease-modifying effects of glucosamine HCl involving regulation of metalloproteinases and chemokines activated by interleukin-1beta in human primary synovial fibroblasts.

The purpose of this study was to investigate the possible involvement of synovium in cartilage destruction in osteoarthritis (OA) patients. Using human primary synovial fibroblasts (HPSFs), we examined the effects of glucosamine (GLN) on the regulation of the expression of matrix metalloproteinases (MMP-1, -2, and -13) and chemokines (IL-8, MCP-1, and RANTES) as well as the involvement of MAPK signal pathways (JNK, ERK, and p-38) and the transcription factor of NF-kappaB on the present or absence of interleukin (IL)-1beta. Our experiments showed that protein production and mRNA expressions of MMP-1, MMP-3, MMP-13, IL-8, MCP-1, and RANTES were downregulated by treatment with glucosamine in HPSFs. The results further showed that GLN could inhibit IkappaBalpha phosphorylation and IkappaBalpha degradation leading to inhibition of the translocation of NF-kappaB to nuclei. However, GLN upregulated MAPKs pathways in HPSFs cells with or without IL-1beta. The results suggest that the inhibition of MMP-1, -3, and -13 expressions as well as IL-8, MCP-1, and RANTES productions by GLN might mediate suppression of NF-kappaB signal pathways, and HPSFs seem to have a potential functions as an alternative source of MMPs and chemokines for inducing the degradation of cartilage in OA.

Ex vivo multiphoton analysis of rabbit corneal wound healing following conductive keratoplasty.

Ex vivo multiphoton imaging is used to characterize rabbit corneal wound healing after conductive keratoplasty (CK) procedures. CK is performed on the right eyes from eight New Zealand albino rabbits while the left eyes are punctured by a keratoplast tip without energy application. Rabbits are humanely sacrificed 1 day, 1, 2, and 4 weeks after the CK procedure. Eye balls are enucleated and placed on the microscope for multiphoton imaging. Multiphoton imaging reveals damage of corneal epithelium and stroma caused by the CK procedure and the subsequent wound healing process can be followed without histological procedures. Multiphoton excited autofluorescence images demonstrate that re-epithelilialization is accomplished within 1 week in both CK and control groups. However, epithelial hyperplasia is observed in CK corneas. In addition, stromal wounds in the control group become inconspicuous within 1 week while obvious wounds still exist in CK corneas for at least 4 weeks. Postconductive keratoplasty corneal damage and wound healing can be characterized by multiphoton microscopy without histological procedures. Our results suggest that multiphoton microscopy has potential in the clinical evaluation of corneal damage due to refractive surgery, and can be used to study and reduce the unwanted side effects of these procedures.

Volume Manipulation Based on 3D Reconstructed Surfaces for Joint Function Evaluation and Surgery Simulation.

In joint surgery, evaluation of the relative positions and angles among joint structures (bones, ligaments, muscle, and cartilages, etc.) in range of motion, lifting and weight bearing of the joint is required. However, current volume visualization techniques provide only static 3D images of anatomic structures in volume data. We propose a method to manipulate (reposition, resize and bend) the joint structures in a volume, by which surgeons can visualize and evaluate the critical positions or angles of the joint structures, and thus plan surgery to correct the morphologic pathology of the joint structures. We also propose a system with a real-time cutting simulation function together with the proposed structure manipulation functions by which surgeons can rehearse and verify joint surgery.

Evidence for a protective role for adiponectin in osteoarthritis.

Obesity has been associated with an increased risk of osteoarthritis (OA). However, the mechanism by which obesity contributes to OA remains uncertain. Adiponectin, an adipocyte-derived hormone, has shown anti-diabetic and anti-atherogenic properties. In the present study, we aimed to investigate the potential role of adiponectin in OA disease. We demonstrated that adiponectin was present in OA synovial fluid (SF) and its expression level was almost 100-fold decrease compared with that in OA plasma. FPLC and ELISA studies revealed the distribution and abundance of the adiponectin complexes in plasma and SF from patients with OA. The percentage of high molecular weight (HMW) per total adiponectin in OA SF was lower than in OA plasma, while that of the hexamer form was similar and the trimer form was higher. The expression levels of adiponectin receptors AdipoR1 and AdipoR2 were examined in human OA tissues by RT-PCR. AdipoR1 was abundantly expressed in cartilage, bone and synovial tissues, whereas AdipoR2 was rarely detected. Finally, the effects of adiponectin on primary chondrocyte functions were studied by using antibody-based protein array and RT-PCR. The patterns of mRNA expression and protein production strongly indicate that adiponectin is involved in the modulation of cartilage destruction in chondrocytes by up-regulating TIMP-2 and down-regulating IL-1beta-induced MMP-13. Together these findings clearly indicate that the adiponectin may act as a protective role in the progression of OA, and this also provide new thinking on the relationship between obesity and OA.

Glenoid and humerus bone analysis using CT transverse sections to automate gleno-humeral joint diagnoses and surgery managements.

This paper describes an image analysis method that evaluates the glenoid and humerus bone morphology to automate the gleno-humeral (GH) joint diagnoses and surgical managements. This method uses radial B-spline curves to approximate ellipse-like shoulder structures including the humeral stem, tubercle and contact joint as well as the glenoid on every CT transverse section. Radius changes from structure centers to bone boundaries are recognized as convex, concave, separate and hole features that are then identified as pathological spurs, fractures and tumors. The centers and radii of these structures from the transverse sections are integrated to determine the properties of the humeral stem and contact joint with the glenoid, including the stem axis as well as the contact joint and glenoid centers, radii and attitudes. Based on the geometric evaluations of these structures and features, the GH joint surgery including tumor dissect and bone graft, open reduction using screws and plate or nails, and arthroplasty are automatically managed to achieve the normal GH joint functions including dissection of tumors, reduction of fractures or dislocations, and free GH joint motions. This prototype system can be used as a qualitative and quantitative tool for the GH joint diseases diagnoses and surgery managements. A series of examples and case studies illustrate the effectiveness of this automated method.

Bone drilling haptic interaction for orthopedic surgical simulator.

Drilling procedure is widely used in orthopedic surgery to position reduced fractured bones and prosthetic components. However, successful execution of bone drilling requires a high level of dexterity and experience, because the drilling resistance is large and sometimes vibrates violently to difficultly grasp the hand-piece or even break the slender drill. This paper introduces haptic functions that are added to a volume based surgical simulator to simulate the drilling process. These haptic functions compute drilling forces and torques based on reliable metal removing theorem. Therefore, accurate prediction for the drilling process can be obtained to provide effective surgery training and rehearsal. A simulation example of screw and plate surgery for positioning the hip trochanter fracture illustrates the practicality and versatility of the proposed method.