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- Appel, Silke, et al.
(författare)
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Potential association of muscarinic receptor 3 gene variants with primary Sjogren's syndrome
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 70:7, s. 1327-1329
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary Sjögren's syndrome (pSS) is characterised by a chronic inflammation of exocrine glands. Salivary gland infiltrates, however, do not correlate well with disease symptoms, and a primary role for the salivary gland parenchyma in disease development has been suggested. Specifically, dysfunction of exocrine pathways involving the muscarinic receptor 3 (CHRM3) has been indicated. Objective: To investigate possible genetic divergence in the CHRM3 gene in patients with pSS. Methods: 530 patients with pSS and 532 controls from a combined Swedish and Norwegian cohort were genotyped for 84 single nucleotide polymorphisms (SNPs) distributed throughout CHRM3. Results: Genetic association was observed with five SNPs localised in intron 3 and 4 of CHRM3, the strongest being rs7548522 (minor allele frequency = 0.06, OR=1.93, 95% CI (1.24 to 3.01); p=0.0033). In addition, clinical parameters, including focus score, abnormal Schirmer's test and presence of autoantibodies, were associated with different SNPs in CHRM3. Conclusion: The study demonstrates a novel association of CHRM3 polymorphisms with pSS, suggesting a functional role for CHRM3 and the salivary gland parenchyma in the pathogenesis of pSS.
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| 4. |
- Sharma, Sunita, et al.
(författare)
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Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactideco-epsilon-caprolactone){poly(LLA-co-CL)} scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.
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