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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling Johannes Keller anita ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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Effects of immune cells on mesenchymal stem cells during fracture healing

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World Journal of Stem Cells 2021年第11期13卷 1667-1695页

作者： Sabrina Ehnert Borna Relja Katharina Schmidt-Bleek Verena Fischer anita ignatius Caren Linnemann Helen Rinderknecht Markus Huber-Lang Miriam Kalbitz Tina Histing Andreas K Nussler Siegfried Weller Research Institute at the BG Trauma Center Tübingen Department of Trauma and Reconstructive SurgeryUniversity of TübingenTübingen 72076Germany Experimental Radiology Department of Radiology and Nuclear MedicineOttovon-Guericke UniversityMagdeburg 39120Germany Julius Wolff Institute and Berlin Institute of Health Center of Regenerative Therapies Charité-University Medicine BerlinBerlin 13353Germany Institute of Orthopedic Research and Biomechanics Ulm University Medical CenterUlm 89091Germany Institute for Clinical and Experimental Trauma-Immunology(ITI) University Hospital UlmUlm 89091Germany Department of Trauma and Orthopedic Surgery University Hospital Erlangen Friedrich-Alexander University Erlangen-Nürnberg(FAU)Erlangen 91054Germany

In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune *** osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone *** are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling *** fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune *** evidence demonstrated that changes of the immune cell composition and function may negatively influence bone *** this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more *** separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between ***,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.

关键词： Trauma Bones Immune response Mesenchymal stem cells Fracture healing

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Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease:A Systematic Review, Meta-Analysis and Meta-Regression

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Chinese Journal of Integrative Medicine 2024年第10期30卷 927-937页

作者： Vito A.Damay ignatius Ivan Department of Cardiovascular Medicine Universitas Pelita Harapan Jakarta Varices Clinic

Background: Resveratrol is a non-flavonoid polyphenol that shows promise in reducing proinflammatory factors and maintaining endothelial function, which hints at its potential role in slowing atherosclerosis and preventing acute coronary events. Objective: To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease(CAD). Methods: A thorough search was conducted in databases(Cochrane Library, Pro Quest, Pub Med, LILACS, Science Direct, Springer, Taylor&Francis, CNKI, Wanfang, and Weipu) until September 24, 2023. The vasopro-inflammatory mediators, endothelial function and outcomes related to cardiovascular events were observed. Titles and abstracts were assessed, and bias was evaluated with Cochrane Ro B 2.0. Heterogeneity of results was explored by metaregression, certainty of evidence was assessed by the GRADE system, and conclusive evidence was enhanced by trial sequence analysis. Results: Ten randomized controlled trials and 3 animal studies investigated resveratrol's impact on inflammatory mediators and endothelial function. In primary prevention studies, meta-analysis showed a significant reduction(95% CI: –0.73 to –0.20; P=0.0005) in tumor necrosis factor-α(TNF-α) expression with resveratrol, demonstrating a dose-dependent relationship. No significant difference was observed in interleukin-6(IL-6) expression with P=0.58 for primary prevention and P=0.57 for secondary prevention. Vascular endothelial nitric oxide synthase(e NOS) expression was significantly increased after resveratrol pre-treatment following CAD events. Secondary prevention studies yielded no significant results; however, meta-regression identified associations between age, hypertension, and lower doses with the extent of TNF-α alterations. High certainty of evidence supported TNF-α reduction, while evidence for IL-6 reduction and e NOS elevation was deemed low. Conclusions: Resveratrol reduces TNF-α in individ

关键词： anti-inflammation coronary artery disease nitric oxide resveratrol systematic review

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Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing

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Bone Research 2022年第3期10卷 469-481页

作者： Mubashir Ahmad Benjamin Thilo Krüger Torsten Kroll Sabine Vettorazzi Ann-Kristin Dorn Florian Mengele Sooyeon Lee Sayantan Nandi Dilay Yilmaz Miriam Stolz Naveen Kumar Tangudu David Carro Vázquez Johanna Pachmayr Ion Cristian Cirstea Maja Vujic Spasic Aspasia Ploubidou anita ignatius Jan Tuckermann Institute of Comparative Molecular Endocrinology(CME) Ulm UniversityHelmholtzstrasse 8/189081 UlmGermany Institute of Orthopedic Research and Biomechanics Ulm UniversityHelmholtzstrasse 1489081 UlmGermany Leibniz Institute on Aging–Fritz Lipmann Institute(FLI) Beutenbergstrasse 11D-07745 JenaGermany Praxisklinik für Orthopädie Unfall-und Neurochirurgie Prof.Bischoff/Dr.Spies/Dr.Mengele89231 Neu-UlmGermany Paracelsus Medizinische Privatuniverstät Institute of PharmacyStrubergasse 215020 SalzburgAustria Department of Endocrinology Ludwig Maximilians University MunichMunich 80336Germany Present address:Institute of Orthopedic Research and Biomechanics Ulm UniversityHelmholtzstrasse 1489081 UlmGermany Present address:UPMC Hillman Cancer Center Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh5115 Center Avenue15232 PittsburghPAUSA Present address:TAmiRNA GmbH Leberstrasse 201110 ViennaAustria

Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5(Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by si RNA, genetic deletion using the Cre-lox P system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.

关键词： Cdk5 healing expression

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Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo

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Journal of Biomaterials and Nanobiotechnology 2015年第1期6卷 20-35页

作者： Jan Henrik Sorensen Lutz Durselen Ken Welch Torben Christian Sorensen Philip Procter Hakan Engqvist Maria Stromme anita ignatius Hartwig Steckel Department of Pharmaceutics and Biopharmaceutics Christian-Albrechts UniversityKielGermany Institute of Orthopaedic Research and Biomechanics Centre of Musculoskeletal ResearchUlmGermany Division for Nanotechnology and Functional Materials The Angstrom LaboratoryUppsala UniversityUppsalaSweden Stryker Trauma GmbH SchonkirchenGermany Stryker Trauma AG SelzachSwitzerland Division for Applied Materials Sciences The Angstrom LaboratoryUppsala UniversityUppsalaSweden

The early fixation of bone screws after surgical implantation still remains a challenge in the field of traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants;their removal at a later time-point may be problematic. An HA coating has been developed to demonstrate that both implant fixation and safe removal are feasible in the same design. Accordingly the aim of this study was to compare the In-Vivo performance of thin biomimetic HA coated titanium screws to uncoated counterparts used as control after bilateral implantation in the femoral condyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, by histology, micro-CT and biomechanically at both two and six weeks post-implantation. The HA coated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrated a significant increase in removal torque values as well as a strong trend towards higher pull-out forces. In addition histology confirmed a higher degree of osseointegration and direct bone to implant contact. At six weeks no difference in pull-out force and removal torque could be detected. SEM images confirmed the absence of any residual HA coating indicating a fast coating degradation In-Vivo. The low level of removal torque after full osseointegration at 6 weeks supports the feasibility of safe and easy removal of the implant. The HA coating under study appears to offer a unique characteristic of enhanced fixation with a minimal increase in removal torque after full osseointegration. This may be of value in clinical applications where it is necessary to assure both screw fixation and later removal.

关键词： Biomimetic Hydroxyapatite In-Vivo Screw Implant Removal Pull-Out Force Removal Torque

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Enhanced Species Diversity Unlocked by Habitat Conservation in Agricultural Landscapes: New Perspectives on Ecological Weed Management and Sustainable Intensification—Species Diversity and Habitat Conservation

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Open Journal of Ecology 2024年第8期14卷 585-603页

作者： Michael ignatius Ferreira Directorate Plant Sciences Western Cape Department of Agriculture Elsenburg South Africa

The impulse to remain profitable by increasing agricultural production levels in view of the greater demand for food, provided impetus to production intensification. The aim of this review is to summarise current literature, reporting specifically on the impact of production intensification on habitats and yield constraints caused by weeds. Secondly, in alleviating these effects over the short term, ecological measures that enhance species diversity in conserved habitats and promote semi-natural habitats in the agricultural landscape, are discussed. In large-scale intensive agriculture, weed control is predominantly rooted in agrochemical applications in the form of herbicides. Long lasting intensive agricultural practices show discord both with the promotion of the biodiversity of microbes belowground and aboveground and with organisms involved in the breaking down of plant material. The presence of native species in the surroundings, in combination with hedgerows and field margins, with a comparatively intricate and balanced variety of plants in a sheltered environment, are essential for settlement of benign insects, particularly in the face of intensive agricultural production. The promising tactic of advantageous seed predators enables decreased herbicide applications. Crop mosaics arranged to advance compatibility at the landscape scale are important to bolster pollination services and insect management, while ecological variety in the surroundings acts as a safety net for habitat diversity. Weed control in combination with different tactics of vegetation use, comprising cover cropping, hedgerows and field margins, sets up safe havens in the landscape, and improves the diffusion of complementary life forms. Field margins perform a meaningful natural function as point of provision for forage, safe havens and distribution passageways for pollinators and insect predators. Production practices that promote more heterogeneity and combine high density semi-natural sa

关键词： Crop mosaics Field Margins Hedgerows Microbial Nitrogen Immobilization Semi-Natural Habitats Soil Microbes Weed Cross-Resistance Weed Seed Predation

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Socioeconomic Distribution of Health and Health Care Utilization in a New Town in Hong Kong, China

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Biomedical and Environmental Sciences 2004年第2期17卷 234-245页

作者： TAK SUN ignatius YU TZE WAI WONG Department of Community and Family Medicine the Chinese University of Hong Kong Shatin N. T. Hong Kong SAR ChinaDepartment of Community and Family Medicine the Chinese University of Hong Kong Shatin N. T. Hong Kong SAR China

Objectives To assess the association of socioeconomic indicators with various chronic and acute illnesses and the utilization of public health care in a new town in Hong Kong, China. Methods Illness experience and socioeconomic and demographic data of 7570 residents from 2022 randomly selected households were collected through telephone interviews. The relationships between socioeconomic indicators and illnesses/choice of health care were explored using stepwise logistic regressions after adjusting for sex and age. Results Significant positive associations were noted between low household income and diabetes mellitus, any chronic illnesses among adults and flu among younger subjects; low educational level and accident-related illness among adults; being born in Chinese mainland and flu, any acute illness in adults. For the utilization of public health care, low household income was the most consistent risk factor. Conclusion This study did not demonstrate a unidirectional socioeconomic gradient in healt

关键词： Socioeconomic indicators Health status Health care need Health care utilization

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Analysis of cost effective pavement treatment and budget optimization for arterial roads in the city of Chattanooga

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Frontiers of Structural and Civil Engineering 2018年第3期12卷 291-299页

作者： Mbakisya ONYANGO Saliha Ammour MERABTI Joseph OWINO ignatius FOMUNUNG Weidong WU Department of Civil Engineering University of Tennessee at Chattanooga Chattanooga TN 37403 USA

Many transportation agencies lack sufficient funds to maintain and repair roads, which results into increased pavement maintenance cost. Pavement Management System （PMS） has demonstrated to be an essential tool for proper management of infrastructure and proper utilization of available funds. The University of Tennessee at Chattanooga utilized Micropaver software as PMS tool to conduct a pavement management analysis of principal arterials in the City of Chattanooga. The study used the City of Chattanooga pavement database to create the current and future pavement conditions. Maintenance and repair （M＆R） planning analysis was also performed in order to determine the most cost-effective treatment and suggest the optimum utilization of funds for the city. An analysis of five budget scenarios was conducted for a five-year plan using the critical pavement condition index （PCI） method （ASTM D6433）. Results show that the backlog elimination budget would be the best scenario because it increases the pavement condition and eliminates the backlog of major maintenance and repairs over the five-year period. The unlimited budget seems though ideal, it does not improve pavement condition. Maintaining current condition and limited budget scenarios would increase both the backlog and the total cost of maintenance and repairs over the analysis period.

关键词： PMS Micropaver pavement budget maintenance rehabilitation

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Identification of groundwater potential in hard rock aquifer systems using Remote Sensing, GIS and Magnetic Survey in Veppanthattai, Perambalur, Tamilnadu

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Journal of Groundwater Science and Engineering 2022年第4期10卷 367-380页

作者： Muthamilselvan A Anamika Sekar Emmanuel ignatius Department of Remote Sensing Bharathidasan UniversityKhajamalai CampusTiruchirappalliTamil Nadu-620023India

Water is an essential natural resource without which life wouldn’t *** study aims to identify groundwater potential areas in Vepapanthattai taluk of Perambalur district,Tamil Nadu,India,using analytic hierarchy process(AHP)*** sensing and magnetic parameters have been used to determine the evaluation indicators for groundwater occurrence under the ArcGIS *** occurrence is linked to structural porosity and permeability over the predominantly hard rock terrain,making magnetic data more relevant for locating groundwater potential zones in the research ***-SW and NW-SE trending magnetic breaks derived from reduction to pole map are found to be more significant for groundwater *** lineaments rose diagram indicates the general trend of the fracture to be in the NE-SW *** normalised criteria weights acquired using the AHP model was used to reclassify the thematic *** a result,the taluk’s low,moderate,and high potential zones cover 25.08%,25.68%and 49.24%of the study area,*** high potential zones exhibit characteristics favourable for groundwater infiltration and storage,with factors as gentle slope of<3°,high lineament densities,magnetic breaks,magnetic low zones as indicative of dykes and cracks,lithology as colluvial deposits and land surface with dense *** depth of the fracture zones was estimated using power spectrum and Euler Deconvolution *** groundwater potential mapping results were validated using groundwater level data measured from the wells,which indicated that the groundwater potential zoning results are consistent with the data derived from the real world.

关键词： Groundwater exploration Remote Sensing and GIS Magnetic data Hard rock terrain Analytical hierarchy process Radially averaged power spectrum

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Inhibition of Mahkota Dewa(Phaleria macrocarpa) bioactive fraction on proliferation of human retinoblastoma tumor cells Y-79 through suppression of mRNA level of cyclin E

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Asian Pacific Journal of Tropical Biomedicine 2017年第4期7卷 280-287页

作者： Nugroho Trilaksana ignatius Riwanto Raymond Rubianto Tjandrawinata Reki Winarto Department of Ophthalmology Faculty of MedicineDiponegoro University Department of Surgery Faculty of MedicineDiponegoro University Division of Molecular Pharmacology and Phytochemistry Dexa Laboratories of Biomolecular SciencesDexa Medica Group

Objective: To prove the molecular mechanisms of Mahkota Dewa(Phaleria macrocarpa) in suppressing proliferation of human retinoblastoma cells through suppression of cell cycle's gene-regulators ***: In this study, the molecular mechanism of anti-tumor effect of fractioned extract of Phaleria macrocarpa(DLBS1425) in human retinoblastoma cells Y-79 was investigated by measuring the tumor cells viability, the assessment of population profiles of tumor cells in the cell cycle, and the mRNA concentration of p16, p21, p53, cyclin D,cyclin E, and E2 ***: DLBS1425 showed an inhibition effects towards proliferation of Y-79 cell *** of proliferation was shown by suppression of cell cycle ***1425 downregulated cyclin E, a G1 phase regulator gene of cell cycle, in dosedependent manner without affecting p53–p21 *** the other word, DLBS1425 inhibits cell proliferation through suppression of cyclin E independently towards conventional proliferation ***: Our results suggest that DLBS1425 is a potential anticancer agent which targets genes involved in cell proliferation in human retinoblastoma cells which make it pharmacologically ideal for the prevention and/or treatment of retinoblastoma cancer.

关键词： Phaleria macrocarpa Mahkota Dewa DLBS1425 Retinoblastoma Cyclin E Cell cycle

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