| 1. |
- Lindahl, Katarina, et al.
(författare)
-
Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy
- 2018
-
Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 114, s. 268-277
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.
|
|
| 2. |
- Cosyn, Jan, et al.
(författare)
-
An Exploratory Case-Control Study on the Impact of IL-1 Gene Polymorphisms on Early Implant Failure
- 2016
-
Ingår i: Clinical Implant Dentistry and Related Research. - : John Wiley & Sons. - 1523-0899 .- 1708-8208. ; 18:2, s. 234-240
-
Tidskriftsartikel (refereegranskat)abstract
- Background The association between IL-1 gene polymorphisms and peri-implantitis has been well documented. However, data on the association with early implant failure are scarce. Purpose The objective of this case-control study was to explore the impact of IL-1A (-889), IL-1B (-511), and IL-1B (+3,954) gene polymorphisms on early implant failure in Caucasians Materials and Methods Between September 2004 and August 2007, 461 patients were treated with dental implants at the University Hospital in Ghent, Belgium. Fourteen subjects of this patient group who had experienced one or more early implant failures (within 6 months from implant installation) were recruited as cases. Fourteen controls, matched in terms of age, gender, and smoking habits, with only surviving implants, were selected from the same patient group. Allele and genotype analysis was performed on the basis of a blood sample by Sanger sequencing of polymerase chain reaction products containing the IL-1A (-889), IL-1B (-511), and IL-1B (+3,954) gene polymorphisms Results A significant impact of the IL-1A (-889) T allele (p=.039) and the IL-1B (+3,954) T allele (p=.003) on early implant failure was demonstrated (odds ratios=3.9 and 15.0, respectively). In addition, the genotypic distribution differed significantly between cases and controls for IL-1B (+3,954) (p=.015 ConclusionsThe IL-1B (+3,954) gene polymorphism seems to affect osseointegration. Additional case-control studies in larger patient groups are needed to confirm this observation.
|
|
| 3. |
- De Wilde, Elisabeth A. W. J., et al.
(författare)
-
The soft tissue immunologic response to hydroxyapatite-coated transmucosal implant surfaces : a study in humans
- 2015
-
Ingår i: Clinical Implant Dentistry and Related Research. - : John Wiley & Sons. - 1523-0899 .- 1708-8208. ; 17:S1, s. e65-e74
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate the soft tissue response in humans immunologically and histologically after placement of mini-implants coated with or without nano-size hydroxyapatite coatings. Material and MethodsCommercially pure (cp) titanium mini-implants (n=13) or nano-hydroxyapatite-coated ones (n=12) were randomly placed into partially edentulous jaws. Crevicular fluid was sampled 1week after placement and subjected to quantitative polymerase chain reaction analysis to explore the inflammatory markers. After 8weeks, implants and surrounding soft and hard tissue were trephined, and undecalcified ground sections were prepared. Inflammatory cell accumulation within a defined region of interest in the soft tissue was quantified histomorphometrically. ResultsNo statistically significant differences in immunological response to the different implant surfaces were found for IL-6 (p=.438), TGF-2 (p=.467), MMP-8 (p=.758), CCL-3 (p=.758), IL-8 (p=.771), and IL-1 (0.771). Histomorphometric evaluation presented no statistically significant difference between the two mini-implant surfaces with regards to number of inflammatory cells (p=.669). ConclusionNano-hydroxyapatite-coated surfaces in the transmucosal region yielded similar inflammatory response and is suggested to be as biocompatible as commercially pure titanium surfaces.
|
|
| 4. |
- Renard, Marjolijn, et al.
(författare)
-
Novel MYH11 and ACTA2 mutations reveal a role for enhanced TGF beta signaling in FTAAD
- 2013
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 165:2, s. 314-321
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Thoracic aortic aneurysm/dissection (TAAD) is a common phenotype that may occur as an isolated manifestation or within the constellation of a defined syndrome. In contrast to syndromic TAAD, the elucidation of the genetic basis of isolated TAAD has only recently started. To date, defects have been found in genes encoding extracellular matrix proteins (fibrillin-1, FBN1; collagen type III alpha 1, COL3A1), proteins involved in transforming growth factor beta (TGF beta) signaling (TGF beta receptor 1 and 2, TGFBR1/2; and SMAD3) or proteins that build up the contractile apparatus of aortic smooth muscle cells (myosin heavy chain 11, MYH11; smooth muscle actin alpha 2, ACTA2; and MYLK).Methods and result: In 110 non-syndromic TAAD patients that previously tested negative for FBN1 or TGFBR1/2 mutations, we identified 7 ACTA2 mutations in a cohort of 43 familial TAAD patients, including 2 premature truncating mutations. Sequencing of MYH11 revealed an in frame splice-site alteration in one out of two probands with TAA(D) associated with PDA but none in the series of 22 probands from the cohort of 110 patients with non-syndromic TAAD. Interestingly, immunohistochemical staining of aortic biopsies of a patient and a family member with MYH11 and patients with ACTA2 missense mutations showed upregulation of the TGF beta signaling pathway.Conclusions: MYH11 mutations are rare and typically identified in patients with TAAD associated with PDA. ACTA2 mutations were identified in 16% of a cohort presenting familial TAAD. Different molecular defects in TAAD may account for a different pathogenic mechanism of enhanced TGF beta signaling.(C) 2011 Elsevier Ireland Ltd. All rights reserved.
|
|
| 5. |
- Terhal, Paulien A., et al.
(författare)
-
A Study of the Clinical and Radiological Features in a Cohort of 93 Patients with a COL2A1 Mutation Causing Spondyloepiphyseal Dysplasia Congenita or a Related Phenotype
- 2015
-
Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 167A:3, s. 461-475
-
Tidskriftsartikel (refereegranskat)abstract
- Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n=64), others having SEMD (n=5), Kniest dysplasia (n=7), spondyloperipheral dysplasia (n=2), or Torrance-like dysplasia (n=2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders.
|
|
| 6. |
- Yuan, Hongbo, et al.
(författare)
-
Synthetic fibrous hydrogels as a platform to decipher cell–matrix mechanical interactions
- 2023
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 120:15
-
Tidskriftsartikel (refereegranskat)abstract
- Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell–matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell–matrix interactions and to improve the design of materials for mechanobiology studies.
|
|
