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The minor collagens in articular cartilage

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Protein & Cell 2017年第8期8卷 560-572页

作者： Yunyun Luo DovUe Sinkeviciute Yi He Morten Karsdal Yves Henrotin Ali Mobasheri Patrik Onnerfjord Anne Bay-Jensen Biomarkers & research Nordic Bioscience A/S Herlev Denmark Faculty of Healthy and Medical Sciences University of Copenhagen Copenhagen Denmark Department of Clinical Sciences Medical Faculty Lund University Lund Sweden bone and Cartilage research Unit Institute of Pathology Level 5 Arthropole Liege University of Liege CHU Sart-Tilman4000 Liege Belgium Faculty of Health and Medical Sciences University of Surrey Guildford Surrey GU2 7XH UK arthritis research UK centre for Sport Exercise and Osteoarthritis Arthritis Research UK Centre for Musculoskeletal AgeingResearch Queen's Medical Centre Nottingham NG7 2UH UK

Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type Ⅳ, Ⅵ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and ⅩⅣ, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.

关键词： collagen biomarker arthritis

NOTUM inhibition increases endocortical bone formation and bone strength

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bone research 2019年第1期7卷 54-65页

作者： Robert Brommage Jeff Liu Peter Voge Faika Mseeh Andrea Y.Thompson David G.Potter Melanie K.Shadoan Gwenn M.Hansen Sabrina Jeter-Jones Jie Cui Dawn Bright Jennifer P.Bardenhagen Deon D.Doree Sofia Moverare-Skrtic Karin H.Nilsson Petra Henning Ulf H.Lerner Claes Ohlsson Arthur T.Sands James E.Tarver David R.Powell Brian Zambrowicz Qingyun Liu Lexicon Pharmaceuticals The WoodlandsTXUSA Wntrix HoustonTXUSA PRA Health Sciences RaleighNCUSA University of Pennsylvania PhiladelphiaPAUSA Regeneron Pharmaceuticals TarrytownNYUSA University of Texas HoustonTXUSA centre for bone and arthritis research Institute of MedicineThe Sahlgrenska Academy at University of GothenburgGothenburgSweden centre for bone and arthritis research University of GothenburgGothenburgSweden Biogen CambridgeMAUSA St.Jude Children’s research Hospital MemphisTNUSA MD Anderson Cancer Center HoustonTXUSA Bethyl Laboratories MontgomeryTXUSA Merck RahwayNJUSA Nurix San FranciscoCAUSA

The disability,mortality and costs caused by non-vertebral osteoporotic fractures are *** osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral *** bone is a major determinant of non-vertebral bone *** identify novel osteoporosis drug targets,we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable *** bone thickness was substantially elevated in Notum?/?*** is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not *** orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were *** increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone ***,inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.

关键词： disability osteoporosis fractures

arthritis and the role of endogenous glucocorticoids

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bone research 2020年第3期8卷 249-265页

作者： Eugenie Macfarlane Markus J.Seibel Hong Zhou bone research Program ANZAC Research InstituteThe University of SydneyCamperdownNSWAustralia

Rheumatoid arthritis and osteoarthritis,the most common forms of arthritis,are chronic,painful,and disabling *** both diseases differ in etiology,they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage,bone,and *** the potent anti-inflammatory properties of therapeutic(i.e.,exogenous)glucocorticoids have been heavily researched and are widely used in clinical practice,the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly *** evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in ***,these models indicate that endogenous glucocorticoid signaling in macrophages,mast cells,and chondrocytes has anti-inflammatory effects,while signaling in fibroblast-like synoviocytes,myocytes,osteoblasts,and osteocytes has pro-inflammatory actions in rheumatoid ***,in osteoarthritis,endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive *** these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

关键词： endogenous Together insight

Nanoscale viscoelastic properties and adhesion of polydimethylsiloxane for tissue engineering

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Acta Mechanica Sinica 2014年第1期30卷 2-6页

作者： J.Chen K.E.Wright M.A.Birch School of Mechanical & Systems Engineering Newcastle University arthritis research UK (ARUK) Tissue Engineering centre Institute of Cellular MedicineNewcastle UniversityUK research UK (ARUK) Tissue Engineering centre Institute of Cellular MedicineNewcastle UniversityUK St James’ University Hospital University of Leeds UK

It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range of biopolymers. However, a recent work published in Nature Materials has revealed that MSCs morphology and differen- tiation was unaffected by crosslink density of polydimethyl- siloxane （PDMS）, which remains elusive. To understand such unusual behaviour, we use nanoindentation tests and modelling to characterize viscoelastic properties and sur- face adhesion of PDMS with different base：crosslink ratio varied from 50：1 （50D） to 10：1 （10D）. It has shown that lower crosslink density leads to lower elastic moduli. De- spite lower nanoindentation elastic moduli, PDMS with lowest crosslink density has higher local surface adhesion which would affect cell-biomaterials interactions. This work suggests that surface adhesion is likely another important physical cue to regulate cell-biomaterials interactions.

关键词： Bioploymer- Nanoindentation- Viscoelasticity Surface adhesion

Advances in murine models of breast cancer bone disease

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 158-177页

作者： Penelope D.Ottewell Michelle A.Lawson Department of Oncology and Metabolism Mellanby Centre for Bone ResearchUniversity of SheffieldSheffield S102RXUK

bone is the most prevalent metastatic site for breast cancer affecting~70%of patients with late-stage *** for this condition currently focus on controlling disease progression and limiting tumour-induced damage to bone,thereby playing a valuable role in increasing quality of ***,limited understanding of the interplay between tumour cells and their environment during bone metastasis has impeded the development of curative *** unravel the complex genetic and phenotypic alterations that occur during this process,it would be helpful to have a model in which tumours develop spontaneously at the primary site,spread to bone,undergo a dormancy phase and then,after a fixed timeframe,become re-activated to form osteolytic/mixed lesions in the *** humans,spontaneous metastasis of primary mammary tumours to bone is rare in mice and no syngeneic models of oestrogen receptor positive disease have been *** there is no single model that authentically reproduces all of the genetic and phenotypic changes representative of human bone metastasis,this review discusses the traditional and novel mouse models that are used to study bone metastasis from breast ***,this review focuses on advances that have been made towards making these models more closely related to human disease in an attempt to help researchers select the correct model(s)for their experimental needs with the aim of improving translational efficacy between the laboratory and the clinic.

关键词： Breast cancer bone metastasis mouse models

Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases

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World Journal of Gastroenterology 2007年第5期13卷 785-790页

作者： Karam A Mahdy Hanaa H Ahmed Fathia Mannaa Azza Abdel-Shaheed Medical Biochemistry Department National Research Centre Egypt Hormones Department National Research Centre Egypt Medical Physiology Department National Research Centre Egypt Child Health Department National Research Centre Egypt

AIM： To investigate the association between serum insulin-like growth factor 1 （IGF-1）, osteocalcin, and parathyroid hormone （PTH） levels with the etiology and clinical condition of patients with chronic liver disease. METHODS： Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection： bilharziasis （9 patients）, hepatitis B virus （HBV, 12 patients） and hepatitis C virus （HCV, 29 patients）. The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control ***, HBcAbIgM, HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction （RT-PCR）. Antibllharzial antibodies were detected by indirect haemagglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted. RESULTS： Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin （14.7 ± 0.54 vs 3.6 ± 0.10, P 〈 0.05）, while that for PTH was positively correlated with total protein （70.1 ± 2.17 vs 6.7 ± 0.10, P 〈 0.05） in patients with HCV infection.

关键词： Liver disease bone turnover Insulin-like growth factor-1 Osteocalcin Parathyroid hormone

Assessment of Diagnosis of Osteoporosis Using Traditional Chinese Medical Method

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Assessment of Diagnosis of Osteoporosis Using Traditional Ch...

EFFECTS OF LONG-TERM NAPROXEN TREATMENT ON RAT bone MASS,GEOMETRY,AND STRENGTH

第二次世界中西医结合大会

作者： JCibere HMPrlic AJLehman 汪叔游 JCPrior JMEsdaile 曾广营 The arthritis research centre of Canada University of British Columbia The arthritis research centre of Canada University of British Columbia The arthritis research centre of Canada University of British Columbia Acupuncture and Chinese Health-care Clinica VancouverCanada The arthritis research centre of Canada University of British Columbia The arthritis research centre of Canada University of British Columbia The arthritis research centre of Canada University of British Columbia

＜正＞ Objective:To assess whether Kidney deficiency syndrome（KDS）is associated with osteoporosis（OP）.Methods:Sixty menopausal women,45—65 years old,having bone mineral density（BMD）tested within 2years were enr...

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EFFECTS OF LONG-TERM NAPROXEN TREATMENT ON RAT BONE MASS,GEO...

Dehydroepiandrosterone:a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient

第二届国际骨质疏松研讨会

作者： Y.Jiang J.Zhao R.Van Audekercke J.Dequeker P.Geusens arthritis and Metabolic bone Disease research Unit University Hospitals Pellenberg

INTRODUCTION Since the formulation of the Raisz hypothesis asserting that prostaglandin-E(PGE) was responsible for bone resorption(1),PGE have been the focus of a great number of experimental bone *** stimulates bone resorption and formation,both in vitro(1) and in vivo(2).NSAIDs which block inflammation by inhibiting production of PGE(3),have been proven to be bone resorption inhibitors and partially prevent bone loss induced by ovariectomy(OVX) and temporary

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Burns & Trauma 2019年第1期7卷 248-260页

作者： Conor Bentley Jon Hazeldine Carolyn Greig Janet Lord Mark Foster NIHR Surgical Reconstruction and Microbiology research centre University Hospital BirminghamBirmingham B152WBUK School of Sport Exercise and Rehabilitation SciencesUniversity of BirminghamBirminghamUK MRC-arthritis research UK centre for Musculoskeletal Ageing research Institute of Inflammation and AgeingBirmingham University Medical SchoolBirmingham B152TTUK NIHR Biomedical research centre University Hospital BirminghamBirminghamUK Royal centre for Defence Medicine Birmingham Research ParkBirmingham B152SQUK.

Severe injuries are the major cause of death in those aged under 40,mainly due to road traffic ***,metabolic and immune pathways respond to limit the tissue damage sustained and initiate wound healing,repair and regeneration ***,depending on age and sex,the response to injury and patient prognosis differ *** are catabolic and immunosuppressive and are produced as part of the stress response to injury leading to an intra-adrenal shift in steroid biosynthesis at the expense of the anabolic and immune enhancing steroid hormone dehydroepiandrosterone(DHEA)and its sulphated metabolite dehydroepiandrosterone sulphate(DHEAS).The balance of these steroids after injury appears to influence outcomes in injured humans,with high cortisol:DHEAS ratio associated with increased morbidity and *** models of trauma,sepsis,wound healing,neuroprotection and burns have all shown a reduction in proinflammatory cytokines,improved survival and increased resistance to pathological challenges with DHEA *** supplementation studies,which have focused on post-menopausal females,older adults,or adrenal insufficiency have shown that restoring the cortisol:DHEAS ratio improves wound healing,mood,bone remodelling and psychological ***,there are no DHEA or DHEAS supplementation studies in trauma patients,but we review here the evidence for this potential therapeutic agent in the treatment and rehabilitation of the severely injured patient.

关键词： Dehydroepiandrosterone Dehydroepiandrosterone sulphate Traumatic injury Intensive care Immune Rehabilitation