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Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI. A Danish nationwide register-based cohort study utilizing data from the Danish National Patient Register and the Danish National Prescription Register. All individuals registered with an OI diagnosis in Denmark from 1995 through 2018, along with a reference population matched 1:5 based on sex, birth year, and month. Sub-hazard ratios (SHR) for peptic ulcer disease, diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, constipation, abdominal wall hernia, and other reasons for abdominal discomfort. The study included 864 individuals with OI (472 women) and 4,276 in the reference population (2,332 women). The SHR was significantly increased for ulcer (3.28 [95% CI 2.21–4.28]), constipation (2.67 [1.91–3.74]), and hernia (among women: 1.85 [1.22–2.80]). Higher SHRs were also observed for inflammatory bowel disease, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain. SHRs were not statistically significantly increased for diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, kidney stones or hemorrhoid disease. Individuals with OI have a higher risk of peptic ulcer disease, constipation, hernia among women, inflammatory bowel diseases, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain, compared with the general population. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a group of rare hereditary collagen disorders. Hearing loss (HL) is a known complication linked to changes in the bones of the middle ear seen in OI. We aimed to determine the prevalence, age at debut, incidence, and risk of HL, surgery on bones of the middle ear, and use of hearing aids. A Danish nationwide, register-based cohort study. Data were extracted from the Danish National Patient register. Anyone with an OI diagnosis between January 1st 1977 and December 31st 2018, matched 1:5 with a reference population (Ref.Pop) on birthyear and sex, were included. 864 persons (487 women) with OI were included in the study and 4276 (2330 women) in the Ref.Pop. The sub-hazard ratio (SHR) for any HL was 4.56 [95% CI 3.64–5.71], with a prevalence of 17.0% and 4.0% in the OI cohort and Ref.Pop. Median age at debut was 42 and 58 years, respectively. The risk of otosclerosis and/or surgery was higher in the OI cohort (SHR 22.51 [95% CI 12.62–40.14]), with a median age at debut of 43 and 32 years in the OI cohort and Ref.Pop, respectively. Hearing aid use was more frequent in the OI cohort (SHR 4.16 [95% CI 3.21–5.40]) than in the Ref.Pop. The median age at debut was 45 and 60 years in the OI cohort and Ref.Pop, respectively. Persons with OI have a higher risk and prevalence of HL, hearing aids, and surgery, debuting younger, and prevalence increases with age. [ABSTRACT FROM AUTHOR]

Repair of bone defects can be done using tissue engineering involving a combination of scaffold, stem cells, and growth factors. The natural scaffold that is commonly used is Deproteinized Bovine Bone Material (DBBM), but it is only osteoconductive and not osteoinductive and has slow biodegradation. Another alternative to the scaffold is Freeze Dried Bovine Bone (FDBB) which has better osteoconductive properties and decellularization scaffold called decellularization Freeze-Dried Bovine Bone (dc-FDBB). In the tissue engineering process, scaffold can induce the differentiation of mesenchymal stem cells and osteoprogenitor cells into osteoblasts which then form the bone matrix. The process of osteoblast formation will affect the increase in Collagen type 1 (COL-1) and Alkaline Phosphatase (ALP) genes. The bjective to compare the expression of COL-1 and ALP on FDBB and DBBM scaffolds for bone tissue engineering. The study was an in vitro laboratory experiment on human Umbilical Cord Mesenchymal Stem Cells (hUC-MSC). There were five treatment groups, group 1 immersion of hUC-MSC on basic medium, group 2 immersion of hUCMSC on osteogenic medium, group 3 FDBB on osteogenic medium, group 4 decellularized dcFDBB on osteogenic medium, and group 5 DBBM on osteogenic medium. Furthermore, RT-PCR readings were carried out on the sixth and 12th days, with each sample replicated two times. Data analysis was carried out using the one-way Analysis of Variance (ANOVA) test. As a result Group 1 showed the highest mean of ALP and COL-1 expression compared to other groups on day six and day 12. One-way ANOVA analysis test showed p<0.05 which indicated a significant difference between groups in the expression of ALP and COL-1. In conclusion the FDBB scaffold showed the highest ALP and COL-1 expression when compared to the DBBM and dc-FDBB groups. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the influence of polymorphisms on genes encoding type I collagen and the genetic susceptibility of tendinopathy. Methodology Case-control study involving 242 Brazilian athletes from different sports modalities (55 cases of tendinopathy and 187 controls). The polymorphisms COLIAI (rs1107946) and COLIA2 (rs412777, rs42524, and rs2621215) were analyzed by theTaqMansystem. Odds ratio(OR)withtheir 95% confidence intervals (CIs) were calculated using a nonconditional logistic regression model. Results The mean age was 24.0 ± 5.6 years old and 65.3% were men. Of the 55 cases of tendinopathy, 25.4% had > 1 affected tendon, the most frequent being patellar (56.3%), rotator cuff (30.9%) and elbow or hand flexors (30.9%). Age and amount of time of sports practice were associated with a higher chance of presenting tendinopathy (5 and 8 times, respectively). The frequency of variant alleles in control and case patients, respectively, was: COLIAI rs1107946 24.0 and 29.6%; COLIA2 rs412777 36.1 and 27.8%; rs42524 17.5 and 25.9%; and rs2621215 21.3 and 27.8%. After adjusting for confounding factors (age and years of sports practice), COLIA2 rs42524and rs2621215 polymorphisms were associated with increased risk of tendinopathy (OR = 5.5; 95% CI = 1.2-24.6 and OR = 3.9; IC95% = 1.1-13.5, respectively). The haplotype COLIA2 CGT was associated with low risk for disease development (OR = 0.5; 95%CI = 0.3-0.9). Conclusion Age (≥ 25 years old), time of sports practice (≥ 6years) and polymorphisms in the COLIA2 gene increased the risk of developing tendinopathy.

IntroductionRespiratory insufficiency is a leading cause of death in individuals with osteogenesis imperfecta (OI). However, evaluating pulmonary function in OI presents challenges. Commonly used pulmonary function tests such as spirometry and body plethysmography are sometimes difficult to perform for OI patients, and reference intervals are not always applicable. The forced oscillation technique (FOT) is a patient-friendly method for detecting respiratory abnormalities that requires no effort from the patient.ObjectiveThis study investigates the feasibility of FOT in the evaluation of respiratory function in the clinical management of OI patients.MethodsTwelve OI patients, comprising eight with Sillence OI I, two with OI IV, and two with OI III, underwent spirometry, body plethysmography, and FOT, both pre-and post-administration of salbutamol.ResultsFOT measurements exhibited consistent trends that aligned with spirometry and body plethysmography findings. The resistance at 8 Hz decreased after the administration of salbutamol, indicating that FOT is able to detect bronchial obstruction and its alleviation by medication (p

Using the method of dynamic light scattering, it was found that the rate of collagen cleavage under the influence of bacterial collagenase decreases by almost 4 times when protein molecules are doped with Cr3+ ions, and when the enzyme activator of Zn2+ ions is added, it increases by 1.3 times. Based on the experimental data, the reaction rate constants k1 were calculated. It was found that when collagen molecules are tanned with a chromium salt, it becomes more resistant to degradation in solutions containing zinc ions than in solutions with the addition of calcium ions, as we described in earlier works. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is the first stage of liver disease, and can progress to a chronic status, such as cirrhosis or hepatocellular carcinoma. Excessive production of extracellular matrix (ECM) components plays an important role in the development of fibrosis. Mechanistically, transforming growth factor beta (TGFβ)-induced phosphorylation of Smad is thought to be a key signaling pathway in the development of liver fibrosis. Although the natural isoquinoline alkaloid oxoglaucine (1,2,9,10-tetramethoxy-7H-dibenzo(de,g)quinolin-7-one) exerts numerous beneficial effects, including anti-cancer, anti-inflammatory, and anti-osteoarthritic effects in diverse cell types, the effects of oxoglaucine on liver fibrosis and fibrogenic gene expression have not been fully elucidated. The aim of this study is to evaluate the signaling pathway and antifibrotic activity of isoquinoline alkaloid oxoglaucine in TFGβ-induced hepatic fibrosis in vitro. Using Hepa1c1c7 cells and primary hepatocytes, we demonstrated that oxoglaucine treatment resulted in inhibition of the expression of fibrosis markers such as collagen, fibronectin, and alpha-SMA. Subsequent experiments showed that oxoglaucine suppressed TGFβ-induced phosphorylation of Smad2 and reactive oxygen species (ROS) generation, without altering cell proliferation. We further determined that the increase in Smad7 by oxoglaucine treatment is responsible for the inhibition of Smad2 phosphorylation and the anti-fibrogenic effects. These findings indicate that oxoglaucine plays a crucial role in suppression of fibrosis in hepatocytes, thereby making it a potential drug candidate for treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Endra Yustin Ellistasari,1 Harijono Kariosentono,2 Bambang Purwanto,3 Brian Wasita,4 Risya Cilmiaty Arief Riswiyant,5 Eti Poncorini Pamungkasari,6 Soetrisno Soetrisno7 1Doctoral Program of Medical Sciences Department, Sebelas Maret University, Surakarta, Indonesia; 2Dermatology and Venereology Department, Sebelas Maret University, Surakarta, Indonesia; 3Internal Medicine Department, Sebelas Maret University, Surakarta, Indonesia; 4Anatomical Pathology Department, Sebelas Maret University, Surakarta, Indonesia; 5Dentistry Department, Sebelas Maret University, Surakarta, Indonesia; 6Public Health Department, Sebelas Maret University, Surakarta, Indonesia; 7Obstetric and Gynecology Department, Sebelas Maret University, Surakarta, IndonesiaCorrespondence: Endra Yustin Ellistasari, Dermatology and Venereology Department, Dr Moewardi General Hospital/Faculty of Medicine Sebelas Maret University, Jl Kol Sutarto 132 Jebres, Surakarta, Central Java, Indonesia, Tel +62 271634634, Email endra_yustin@yahoo.comPurpose: This is an in-vitro experimental study to analyze the effect of Exo-HUVEC on endothelial cell (CD31), cell proliferation, matrix metalloproteinase 1 (MMP-1) and collagen type 1 on irradiated fibroblast with UVB as photo-aging model.Patients and Methods: Fibroblast cultures were divided into 5 groups, namely without UVB exposure, UVB exposure 600mJ/cm2 for 80 seconds as photo-aging model, and UVB exposure +Exo-HUVEC exposure 0.1%, 0.5% and 1%. The endothelial cell was stained with a CD31 marker, MMP-1 were examined with ELISA, cell proliferation is detected using an MTT assay; meanwhile, collagen type 1 deposition and endothelial cell were measured using flowcytometry.Results: This study found positive endothelial cell marker CD31. Significant difference was found in cell proliferation, MMP-1 and collagen type 1 level between the control group with UVB irradiation and the treatment group with Exo-HUVEC (p < 0.05).Conclusion: Exo-HUVEC significantly increases cell proliferation and collagen type 1 level, while decrease MMP-1 levels on irradiated fibroblast; therefore, Exo-HUVEC ameliorate the photo-aging of skin fibroblast.Graphical Abstract: Keywords: photo-aging, Exo-HUVEC, endothelial cell, cell proliferation, MMP-1, collagen type 1

Abstract Introduction Bladder outlet obstruction (BOO) was caused by a series of histological and biochemical changes in the bladder wall, through the inflammation process in the bladder wall, hypertrophy and fibrosis. ADSC has an important role in bladder regeneration. Methods and materials This study was an experimental randomized study using male Wistar rats which were monitored at 2 and 4 weeks to determine the effect of ADSC therapy on TGF-β1 type I collagen, and degree of fibrosis. Result Rats were divided into 5 groups. In the week 2 BOO group, 1 sample included in the category of moderate fibrosis, 1 sample that was given ADSC with mild fibrosis category, 3 samples included in severe fibrosis category, 3 samples that were given ADSC included in the category of moderate fibrosis. The concentration of TGF-β1 in the hADSC therapy group was significantly lower than the control group at the 2nd and 4th week of monitoring (p2 = 0.048, p4 = 0.048), and also with more type I collagen on 2nd and the 4th week (p2 = 0.048, p4 = 0.048). Conclusion ADSC therapy can reduce the concentration of TGF-β1, type I collagen, and degree of fibrosis in the male Wistar BOO model.

The present study was conducted to examine the bioactive and wound healing properties of collagen hydrolysate derived from Piaractus brachypomus (pacu) fish skin waste. Collagen type I (P coll.) yielding 72.25% was isolated from skin waste by following acid-soluble collagen extraction method. Further, collagen was fragmented using bacterial collagenase and the processed collagen hydrolysate (peptides) was in the range of 10–15 kDa that was further purified using ion-exchange chromatography. The FTIR spectra of both P coll. and collagen hydrolysate (PSCH) were nearly similar showing that PSCH retained the structural and chemical composition similar to its parent molecule (P coll.). Solubility analysis revealed that PSCH has slightly better solubility compared to P coll. Similarly, scanning electron micrographs also exhibited more uniform and porous microstructure of PSCH compared to P coll. Further, PSCH was found to be efficient in peroxide quenching (64.5%) and radical scavenging activities (85.74%). MTT studies confirmed PSCH to be non-toxic displaying 84.68% cell viability at the highest concentration (3 mg/ml) and hemocompatibility test revealed PSCH to be non-hemolytic with minimal lysis of only 2.1% of human RBCs. In addition, PSCH also displayed a remarkable wound closure ability of more than 80% at 12 h and 100% within 24 h. Hence, these findings suggest that recycled PSCH has potent wound healing ability and can be produced economically on a large scale for possible biological applications in regenerative medicine. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the available literature and, using a modified Delphi approach, the development of a series of statements summarizing current knowledge. Fourteen clinical recommendations were developed to guide clinicians, patients, and stakeholders about an approach for CVD in adults with OI. This paper describes how the work was conducted and provides the background and rationale for each recommendation. Furthermore, we highlight knowledge gaps and suggest research priorities for the future study of CVD in OI., (© The Author(s) [2024]. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Objective: Bladder cancer is the 9th leading cause of human urologic malignancy and the 13th cause of death worldwide. Increased collagen cross-linking, NIDOGEN1 expression and consequently stiffness of extracellular matrix (ECM) may be responsible for the mechanotransduction and regulation of transcriptional co-activator with PDZ-binding motif (TAZ) and transforming growth factor β1 (TGF-β1) signaling pathways, resulting in progression of tumorigenesis. The present study aimed to assess whether type 1 collagen expression is associated with TAZ nuclear localization. Materials and Methods: In this case-control study, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis were performed to evaluate the activation of the TAZ pathway in patients with bladder cancer (n=40) and healthy individuals (n=20). The ELISA method was also conducted to measure the serum concentrations of TGF-β1. Masson’s trichrome staining was carried out to histologically evaluatethe density of type 1 collagen. Results: Our findings that the expression levels of COL1A1, COL1A2, NIDOGEN1, TAZ, and TGF-β1 genes were overexpressed in patients with bladder cancer, and their expression levels were positively associated with the grade of bladder cancer. The immunohistochemical analysis demonstrated that the nuclear localization of TAZ was markedly correlated with high-grade bladder cancer. We also found that TAZ nuclear localization was substantially higher in cancerous tissues as compared with normal bladder tissues. Masson's trichrome staining showed that the tissue density of type I collagen was considerably increased in patients with bladder cancer as compared with healthy subjects. Conclusion: According to our findings, it seems the alterations in the expression of type I collagen and NIDOGEN1, as well as TAZ nuclear localization influence the progression of bladder cancer. The significance of TGF-β1 and TAZ expression in tumorigenesis and progression to high-grade bladder cancer was also highlighted. However, a possible relationship between TGF-β1 expression and the Hippo pathway needs further investigations.

Infantile cortical hyperostosis or Caffey disease is a rare genetic disorder caused by a mutation in the collagen 1 gene. The mechanism of the disease has not yet been fully elucidated, but the most important factor in the pathogenesis and the consequence of the mutation is periosteal inflammation. The disease becomes clinically evident during the first months of life with asymmetrical bone thickening, most commonly in the mandible, clavicle, scapula, ribs, and long bones. Non-specific systemic inflammatory symptoms can also be present. X-ray imaging with demonstration of bone hyperostosis is essential for the diagnosis, which is confirmed by genetic testing. Treatment is symptomatic. The prognosis of the disease depends on the mode of inheritance. The autosomal recessive form, known as the prenatal form, has a poor prognosis. The autosomal dominant form or infantile Caffey disease usually resolves spontaneously without consequences before the age of two years. We present a case of a neonate with Caffey disease with proven COL1A1 gene mutation.

Hepatic fibrosis is the first stage of liver disease, and can progress to a chronic status, such as cirrhosis or hepatocellular carcinoma. Excessive production of extracellular matrix (ECM) components plays an important role in the development of fibrosis. Mechanistically, transforming growth factor beta (TGFβ)-induced phosphorylation of Smad is thought to be a key signaling pathway in the development of liver fibrosis. Although the natural isoquinoline alkaloid oxoglaucine (1,2,9,10-tetramethoxy-7H-dibenzo(de,g)quinolin-7-one) exerts numerous beneficial effects, including anti-cancer, anti-inflammatory, and anti-osteoarthritic effects in diverse cell types, the effects of oxoglaucine on liver fibrosis and fibrogenic gene expression have not been fully elucidated. The aim of this study is to evaluate the signaling pathway and antifibrotic activity of isoquinoline alkaloid oxoglaucine in TFGβ-induced hepatic fibrosis in vitro. Using Hepa1c1c7 cells and primary hepatocytes, we demonstrated that oxoglaucine treatment resulted in inhibition of the expression of fibrosis markers such as collagen, fibronectin, and alpha-SMA. Subsequent experiments showed that oxoglaucine suppressed TGFβ-induced phosphorylation of Smad2 and reactive oxygen species (ROS) generation, without altering cell proliferation. We further determined that the increase in Smad7 by oxoglaucine treatment is responsible for the inhibition of Smad2 phosphorylation and the anti-fibrogenic effects. These findings indicate that oxoglaucine plays a crucial role in suppression of fibrosis in hepatocytes, thereby making it a potential drug candidate for treatment of liver fibrosis.

Patients with Osteogenesis Imperfecta (OI) have varying degrees of bone fragility and increased fracture rates. There is a paucity of data related to complications to pregnancies in patients with OI and to their offspring. With this study we aim to evaluate the risk of complications to pregnancies, delivery, and offspring in pregnancies where the mother or father have OI. Nationwide, register-based, cohort study. Danish health register-based data. All pregnancies registered in the Danish health registers where one parent has OI and a reference population of all other pregnancies in the general population from 1997 to 2018. Descriptive epidemiology Pregnancy and delivery complications (e.g. prevalence of pre-eclampsia, eclampsia and perinatal haemorrhage), and complications in the offspring (e.g. prevalence of low birth weight, low Apgar Score, need of CPAP or NICU, prevalence of congenital malformations (using the EUROCAT classification), incidence of osteogenesis imperfecta, prevalence of birth related fractures and hospital contacts during the first year of life) from pregnancies with parental OI. We identified 433 OI related pregnancies among 134 mothers with OI and 73 fathers with OI. The rates of pregnancy and delivery complications were similar between the OI cohorts and the reference population. More (31 % vs 19 %) children were delivered by caesarean section in the OI cohort than in the reference population. Pregnancies, where one parent have OI, result in live births to term with very few complications. • Fear of complications to the mother and risk of complications to the outcome may be a barrier for some patients with OI. • In mothers with OI, most pregnancies are without complications and go full term and results in healthy children. • This is the first nationwide, register based, cohorts study evaluating pregnancy risk in patients with OI. [ABSTRACT FROM AUTHOR]

Introduction: Bladder outlet obstruction (BOO) was caused by a series of histological and biochemical changes in the bladder wall, through the inflammation process in the bladder wall, hypertrophy and fibrosis. ADSC has an important role in bladder regeneration.Methods and Materials: This study was an experimental randomized study using male Wistar rats which were monitored at 2 and 4 weeks to determine the effect of ADSC therapy on TGF-β1 type I collagen, and degree of fibrosis.Result: Rats were divided into 5 groups. In the week 2 BOO group, 1 sample included in the category of moderate fibrosis, 1 sample that was given ADSC with mild fibrosis category, 3 samples included in severe fibrosis category, 3 samples that were given ADSC included in the category of moderate fibrosis. The concentration of TGF-β1 in the hADSC therapy group was significantly lower than the control group at the 2nd and 4th week of monitoring (p2 = 0.048, p4 = 0.048), and also with more type I collagen on 2nd and the 4th week (p2 = 0.048, p4 = 0.048).Conclusion: ADSC therapy can reduce the concentration of TGF-β1, type I collagen, and degree of fibrosis in the male Wistar BOO model. [ABSTRACT FROM AUTHOR]

In this study, a comparative structural and bioactive analysis of collagen extracted from the skin of bony and cartilaginous fishes. The acid-soluble method was followed to extract the collagen from Hypophthalmichthys molitrix (silver carp) and Rhizoprionodon acutus (milk shark) followed by purification using Ion exchange chromatography. A higher yield of collagen was obtained from the skin of SCsk (69.45%) as compared to SHsk (55.29%). SDS PAGE displayed the characteristic α, β bands of the collagen type1. The native conformation and secondary structure stability of collagen were confirmed by FTIR, XRD and CD studies. The SEM micrographs exhibited the layered and fibrillar nature of the collagen from SHsk and SCsk, respectively. Relative solubility and thermal denaturation analysis showed SCsk to be more stable, but SHsk could withstand higher temperatures. 53.65% of antioxidant activity was observed in SCsk collagen as compared to SHsk (45.9%). Haemocompatibility, cell viability and adhesion results also displayed silvercarp skin to be a better source than Shark skin collagen. The results establish the potential of silver carp collagen as a biomaterial that can have many commercial applications in tissue engineering, cosmetics and food industries. [ABSTRACT FROM AUTHOR]

Study Design Retrospective study. Purpose This study aimed to assess the effect of refilling with hydroxyapatite/collagen (HAp/Col) composite on an iliac crest defect after spinal fusion. Overview of Literature The use of iliac crest bone graft has been the gold standard in spinal fusion for a long time because of its biological and non-immunologic properties. Few reports have addressed how bone defects recover after iliac crest bone harvest following spinal fusion. Methods Cancellous bone was collected from the anterior iliac crest during lateral interbody fusion (LIF), and the bone void of the ilium was refilled with a porous HAp/Col composite. We assessed bone recovery using computed tomography (CT). From the 74 patients who underwent LIF between January 2015 and December 2016, we included 49 patients whose iliac crest could be evaluated using CT at 3 months and 1 year after the surgery. Results Bone defects decreased in a time-dependent manner after the surgery. Cortical closure was observed in 28.5% of the cases 3 months after the surgery; at 1 year postoperatively, 95.9% of the patients had cortical closure. Complete repair of the cancellous bone was achieved in 57.1% of the patients at 3 months after the surgery and in 95.9% at 1 year after the surgery. There were no significant hematomas, infections, iliac crest fractures, or soft tissue herniation. Conclusions Radiographic recovery of cortical and cancellous bone defects was achieved with high probability via refilling with HAp/Col composite over the 1-year period.

Background: On stopping bisphosphonate treatment, bone resorption may increase before evidence of a decrease in bone density. Offset of bisphosphonate effect may therefore be monitored by measuring C-terminal telopeptide (CTX) following long-term bisphosphonate treatment to inform clinical decisions on drug holiday. Methods: Retrospective analysis of 158 patients (83% female, mean age 71 years) starting a drug holiday had plasma CTX measured at discontinuation (baseline), n=138 and 4 months and n=136, and 12 months (n=100). Premenopausal mean CTX levels and the least significant change (LSC) detectable were used to define target thresholds for bone turnover. Results: Following long-term bisphosphonate treatment (69% alendronic acid, 33% risedronate, mean duration 8 years SD 2.7), 32% patients had CTX above target (0.19 μg/L). In those with baseline CTX below threshold, 28% increased CTX to >0.19 μg/L and > LSC (0.06 μg/L) by 4 months (mean CTX increase 0.05 μg/L [95% confidence interval (CI): 0.04–0.06; p

The extracellular matrix (ECM) is a complex fibrillar network that couples a cell with its environment and directly regulates cells’ functions via structural, mechanical, and biochemical signals. The goal of this study was to engineer and characterize ECM-mimicking protein platforms with material properties covering both physiological and pathological (tumorous) tissues. We designed and fabricated three-dimensional (3D) fibrillar scaffolds comprising the two major components of the ECM, namely collagen (Col) and fibronectin (Fn), using a previously developed freeze-drying method. While scaffolds porous architecture and mechanics were controlled by varying Col I concentration, Fn deposition and conformation were tuned using varied immersion temperature and assessed via intramolecular Förster Resonance Energy Transfer (FRET). Our data indicate that all scaffolds were able to support various crucial cellular functions such as adhesion, proliferation and matrix deposition. Additionally, we show that, keeping the stiffness constant and tuning the conformation of the Fn layer used to coat the Col scaffolds, we were able to control not only the invasion of cells but also the conformation of the matrix they would deposit, from a compact to an unfolded structure (as observed in the breast tumor microenvironment). Therefore, these tunable scaffolds could be used as 3D cell culture models, in which ECM microarchitecture, mechanics and protein conformation are controlled over large volumes to investigate long-term mechanisms such as wound healing phases and/or vascularization mechanisms in both physiological and pathological (tumorous) microenvironments. These findings have implications for tissue engineering and regenerative medicine.

Objective: Bladder cancer is the 9th leading cause of human urologic malignancy and the 13th cause of death worldwide. Increased collagen cross-linking, NIDOGEN1 expression and consequently stiffness of extracellular matrix (ECM) may be responsible for the mechanotransduction and regulation of transcriptional co-activator with PDZ-binding motif (TAZ) and transforming growth factor β1 (TGF-β1) signaling pathways, resulting in progression of tumorigenesis. The present study aimed to assess whether type 1 collagen expression is associated with TAZ nuclear localization. Materials and Methods: In this case-control study, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis were performed to evaluate the activation of the TAZ pathway in patients with bladder cancer (n=40) and healthy individuals (n=20). The ELISA method was also conducted to measure the serum concentrations of TGF-β1. Masson’s trichrome staining was carried out to histologically evaluate the density of type 1 collagen. Results: Our findings that the expression levels of COL1A1, COL1A2, NIDOGEN1, TAZ, and TGF-β1 genes were overexpressed in patients with bladder cancer, and their expression levels were positively associated with the grade of bladder cancer. The immunohistochemical analysis demonstrated that the nuclear localization of TAZ was markedly correlated with high-grade bladder cancer. We also found that TAZ nuclear localization was substantially higher in cancerous tissues as compared with normal bladder tissues. Masson's trichrome staining showed that the tissue density of type I collagen was considerably increased in patients with bladder cancer as compared with healthy subjects. Conclusion: According to our findings, it seems the alterations in the expression of type I collagen and NIDOGEN1, as well as TAZ nuclear localization influence the progression of bladder cancer. The significance of TGF-β1 and TAZ expression in tumorigenesis and progression to high-grade bladder cancer was also highlighted. However, a possible relationship between TGF-β1 expression and the Hippo pathway needs further investigations. [ABSTRACT FROM AUTHOR]

Background: Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy. Methods: Various concentrations of dextrose and lidocaine were treated in NIH-3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis. Results: The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I. Conclusions: D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation. [ABSTRACT FROM AUTHOR]

Bioactive glasses (BG) are known for their unique ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not sufficient to produce bone consolidation. The use of composite materials may constitute an optimized therapeutical intervention for bone stimulation. The aim of this study was to characterize BG/collagen/poly (d , l -lactic- co -glycolic) acid (BG/COL/PLGA) composites, in vitro biocompatibility and in vivo biological properties. MC3T3-E1 cells were evaluated by cell proliferation, ALP activity, cell adhesion and morphology. Qualitative histology and immunohistochemistry were performed in a calvarial bone defect model in rats. The in vitro study demonstrated, after 3 and 6 days of culture, a significant increase of proliferation was observed for BG/PLGA compared to BG/COL and BG/COL/PLGA. BG/COL/PLGA presented a higher value for ALP activity after 3 days of culture compared to BG/PLGA. For in vivo analysis, 6 weeks post-surgery, BG/PLGA showed a more mature neoformed bone tissue. As a conclusion, the in vitro and in vivo studies pointed out that BG/PLGA samples improved biological properties in calvarial bone defects, highlighting the potential of BG/PLGA composites to be used as a bone graft for bone regeneration applications. [ABSTRACT FROM AUTHOR]

Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) exhibits superior biocompatibility and longevity as a dermal filler. We previously developed composite HAc-hydroxyapatite (HAp) fillers. Herein, we systematically compared the protein-level increase and gene expression between HAc-micro-HAp and HAc-nano-HAp in mice and determined the mechanisms underlying the biological responses to HAc and HAp. Five-week-old female BALB/c-nude mice were classified into five groups: normal skin, Radiesse, Restylane, HAc-nano-HAp, and HAc-micro-HAp. Fillers (200 μl) were injected to evenly fill the back of mice. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real-time polymerase chain reaction analysis, and immunohistochemistry were performed to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nano-HAp was determined by hematoxylin and eosin staining after 12 weeks. Protein and gene expression analyses indicated that, compared with pure fillers, HAc-nano-HAp and HAc-micro-HAp hydrogels preferentially promoted collagen and elastic fiber formation through the TGF-β pathway. The composite fillers also exhibited no evidence of organ toxicity. HAc–HAp filler might play an important role in collagen and elastic fiber regeneration. HAc filler stimulates collagen type 1 and elastic fiber synthesis through the TGF-β/Smad pathway. The role of HAc–HAp composite fillers in photoaging in animal models and their effects on skin, including elasticity and tensile strength, should be investigated. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study is to describe shared morphological features of peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF) in detail and discuss the possible relationship between them. Materials and Methods: Ten intermediate cases with features resembling to both POF and PGCG were selected and type 3 and 1 collagen immunostainings were performed for evaluation of the connective tissue maturation. Immunohistochemical staining percentage (SP) for stromal cells in the slides of POF and PGCG counterparts of intermediate lesions was scored as 1 when the SP was above 10%, 2 when the SP was above 25%, 3 when the SP was above 50% and 4 when the SP was above 75%. Staining intensity (SI) of immunuhistochemical staining was graded and scored as 1 - mild, 2 – moderate, and 3 - severe. An immunoreactivity score was calculated by multiplying SP and SI. Results: All intermediate lesions comprised osteoclast type multinucleated giant cells and partly mineralized hard tissue component. Parts of intermediate lesions resembling POF showed higher type 1 collagen immunoreactivity compared to the PGCG counterparts of intermediate lesions (P < 0.05). PGCG counterparts showed higher type 3 collagen immunoreactivity compared to the POF counterparts of the intermediate lesions (P < 0.05). Conclusion: POF may be a later stage lesion with morphologically more mature components. A possible transformation may be considered for these two lesions.

Introduction: Respiratory insufficiency is a leading cause of death in individuals with osteogenesis imperfecta (OI). However, evaluating pulmonary function in OI presents challenges. Commonly used pulmonary function tests such as spirometry and body plethysmography are sometimes difficult to perform for OI patients, and reference intervals are not always applicable. The forced oscillation technique (FOT) is a patient-friendly method for detecting respiratory abnormalities that requires no effort from the patient., Objective: This study investigates the feasibility of FOT in the evaluation of respiratory function in the clinical management of OI patients., Methods: Twelve OI patients, comprising eight with Sillence OI I, two with OI IV, and two with OI III, underwent spirometry, body plethysmography, and FOT, both pre-and post-administration of salbutamol., Results: FOT measurements exhibited consistent trends that aligned with spirometry and body plethysmography findings. The resistance at 8 Hz decreased after the administration of salbutamol, indicating that FOT is able to detect bronchial obstruction and its alleviation by medication ( p  < 0.05). The resonant frequency during expiration was higher than during inspiration in nearly all patients, suggesting obstructive disease. The technique gives insight into both inspiratory and expiratory impairment of pulmonary ventilation. The main FOT parameters showed a relatively high repeatability in duplicate measurements., Conclusion: Bronchial obstruction can be detected by FOT in patients with OI during quiet breathing, making it an easily executable alternative to other lung function measurements. The technique can detect the bronchodilator effect of sympathomimetic medication. It has the potential to provide information on expiratory flow limitation, pulmonary restriction, and reduced lung compliance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Storoni, Verdonk, Micha, Jak, Bugiani, Eekhoff and van den Aardweg.)

Background: Orthodontics of the 21st century requires aesthetic, painless, predictable, and quick treatments. This demand for faster results generated orthodontic movement acceleration protocols (OMAPs); among other OMAPs we present low-level laser (LLL) as a candidate. Objective: To evaluate levels of interleukin (IL)-1, IL-10, and type 1 collagen in the periodontal ligament of first molars of rats subjected to orthodontic traction with and without LLL irradiation, compared with untreated controls (CO), and to evaluate whether the dose of LLL used in this work is eligible as an OMAP. Materials and methods: A total of 35 male Wistar rats were distributed into three groups: group 1 NI (nonirradiated) n = 15, group 2 IR (laser irradiated using 5 J, 177 J/cm2, and 100 mW applied in contact to the vestibular mesial, vestibular distal, and palatal faces of gum tissue around molar region for 50 sec each point, for 3 consecutive days, immediately 24 and 48 h after orthodontic device placement.) n = 15, and group 3 CO n = 5; groups 1 and 2 were subjected to orthodontic force and each group was divided into three subgroups that were sacrificed after 3, 5, and 7 days, IL-1/10 and COL-1 levels were analyzed. Results: In the IR group, levels of IL-1/10 and COL-1 showed peak anticipation after LLL irradiation compared with those in the NI and CO groups. Conclusions: These results can also infer that this dose of LLL can be used as an OMAP. [ABSTRACT FROM AUTHOR]

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Esophageal squamous-cell carcinoma (ESCC) is commonly treated with radiotherapy; however, radioresistance hinders its clinical effectiveness, and the underlying mechanism remains elusive. Here, we develop patient-derived xenografts (PDXs) from 19 patients with ESCC to investigate the mechanisms driving radioresistance. Using RNA sequencing, cytokine arrays, and single-cell RNA sequencing, we reveal an enrichment of cancer-associated fibroblast (CAF)-derived collagen type 1 (Col1) and tumor-cell-derived CXCL1 in non-responsive PDXs. Col1 not only promotes radioresistance by augmenting DNA repair capacity but also induces CXCL1 secretion in tumor cells. Additionally, CXCL1 further activates CAFs via the CXCR2-STAT3 pathway, establishing a positive feedback loop. Directly interfering with tumor-cell-derived CXCL1 or inhibiting the CXCL1-CXCR2 pathway effectively restores the radiosensitivity of radioresistant xenografts in vivo. Collectively, our study provides a comprehensive understanding of the molecular mechanisms underlying radioresistance and identifies potential targets to improve the efficacy of radiotherapy for ESCC. [Display omitted] • Estimation of responsiveness to radiotherapy using ESCC PDX models • CXCL1-mediated collagen deposition confers radioresistance • CAF-derived collagen promotes the secretion of CXCL1 from tumor cells • Targeting collagen synthesis or CXCL1/CXCR2 pathway restores radiosensitivity Yang et al. investigate the mechanisms of radioresistance using well-established ESCC PDX models. They identify a positive feedback loop between tumor-cell-derived CXCL1 and CAF-derived collagen that ultimately leads to radioresistance, providing a potential target to predict and overcome radioresistance. [ABSTRACT FROM AUTHOR]

This impaired lung growth results in the lack of attainment of normal lung size and maximal lung function (Yang et al., [5]). Keywords: alveoli; bronchopulmonary dysplasia; collagen type 1; lung development EN alveoli bronchopulmonary dysplasia collagen type 1 lung development 247 248 2 01/17/23 20230115 NES 230115 Dimori et al. ([1]) present a comprehensive study of pulmonary changes in mouse models of osteogenesis imperfecta (OI). These findings support the concept that the genetic underpinnings of OI are independently associated with abnormal pulmonary development, which is important not only for understanding OI but also for our understanding of lung development. [Extracted from the article]

Objective: Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. Sources: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. Summary of the findings: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X‐linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. Conclusions: Considering the discovery of new genes and limited genotype‐phenotype correlation, the use of next‐generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference.

The design of constructs for tubular tissue engineering is challenging. Most biomaterials need to be reinforced with supporting structures such as knittings, meshes or electrospun material to comply with the mechanical demands of native tissues. In this study, coupled helical coils (CHCs) were manufactured to mimic collagen fiber orientation as found in nature. Monofilaments of different commercially available biodegradable polymers were wound and subsequently fused, resulting in right-handed and left-handed polymer helices fused together in joints where the filaments cross. CHCs of different polymer composition were tested to determine the tensile strength, strain recovery, hysteresis, compressive strength and degradation of CHCs of different composition. Subsequently, seamless and stable hybrid constructs consisting of PDSII® USP 2-0 CHCs embedded in porous collagen type I were produced. Compared to collagen alone, this hybrid showed superior strain recovery (93.5 ± 0.9% vs 71.1 ± 12.6% in longitudinal direction; 87.1 ± 6.6% vs 57.2 ± 4.6% in circumferential direction) and hysteresis (18.9 ± 2.7% vs 51.1 ± 12.0% in longitudinal direction; 11.5 ± 4.6% vs 46.3 ± 6.3% in circumferential direction). Furthermore, this hybrid construct showed an improved Young’s modulus in both longitudinal (0.5 ± 0.1 MPa vs 0.2 ± 0.1 MPa; 2.5-fold) and circumferential (1.65 ± 0.07 MPa vs (2.9 ± 0.3) × 10 −2 MPa; 57-fold) direction, respectively, compared to templates created from collagen alone. Moreover, hybrid template characteristics could be modified by changing the CHC composition and CHCs were produced showing a mechanical behavior similar to the native ureter. CHC-enforced templates, which are easily tunable to meet different demands may be promising for tubular tissue engineering. Statement of Significance Most tubular constructs lack sufficient strength and tunability to comply with the mechanical demands of native tissues. Therefore, we embedded coupled helical coils (CHCs) produced from biodegradable polymers – to mimic collagen fiber orientation as found in nature – in collagen type I sponges. We show that the mechanical behavior of CHCs is very similar to native tissue and strengths structurally weak tubular constructs. The production procedure is relatively easy, reproducible and mechanical features can be controlled to meet different mechanical demands. This is promising in template manufacture, hence offering new opportunities in tissue engineering of tubular organs and preventing graft failure. [ABSTRACT FROM AUTHOR]

The two mesenchymal stem cell (MSC) populations that have gained most attention in relation to bone tissue engineering are adipose tissue (AT) MSCs and bone marrow (BM) MSCs. The purpose of this study was to investigate the ability of human BM-MSCs and AT-MSCs to survive, proliferate and deposit collagen type 1 when cultured on polycaprolactone nanofiber scaffolds and to ascertain the effect of medium composition on collagen type 1 formation and expression of osteogenic genes. The cells were seeded on polycaprolactone nanofiber scaffolds and cultured in three different types of media that differed by the presence of ascorbic acid, β-glycerophosphate and dexamethasone, that are typical components used for osteogenic differentiation of MSCs in vitro . In summary, AT-MSCs were proliferating significantly faster than BM-MSCs. AT-MSCs also showed better ability to deposit collagen type 1 and had a higher expression of early osteogenic markers, whereas BM-MSCs had higher expression of late osteogenic markers. This suggests that MSCs from diverse sources have different attributes and with respect to osteogenic differentiation, AT-MSCs are more immature compared to BM-MSCs. Collagen formation was depending on medium composition and the organization of collagen type 1 appeared to be influenced by the presence of dexamethasone. [ABSTRACT FROM AUTHOR]

Objective To explore the mechanism and effects of globular adiponectin (gAd) on atherosclerosis in rats with type 2 diabetes mellitus (T2DM). Methods Ninety male Sprague-Dawley rats were divided into control group (group N, n=24) and T2DM model group (n=66) according to the method of random number table. Similarly, 53 successful modeling diabetic rats were randomly divided into T2DM group (group D, n=26) and intervention group (group A, n=27). Rats in group A were administrated with gAd in dose of 10 μg·kg-1·d-1, and rats in the other two groups were administrated with saline respectively. At the end of 4, 8 and 12 weeks (w), serum biochemical indexes were tested in 8 rats collected randomly from each group, respectively. In the mean time, atherosclerotic changes of thoracic aorta were observed by HE staining, and the expressions of type 1 collagen (Col-1) were detected by immunohistochemistry. The protein and mRNA expressions of transforming growth factor β1 (TGF-β1), Smad3, Smad7 were detected by Western blotting and real time fluorescent quantitative polymerase chain reaction, respectively. Statistical analysis was performed by using one way analysis of variance and LSD-t test. Results In each period, compared with group N, in group D, atherosclerotic changes of thoracic aorta appeared, the lesions worsened gradually with staining time, and the expressions of TGF-β1, Smad3 and Col-1 increased significantly (12 w: 1.28±0.01 vs 0.99±0.02, 1.08±0.01 vs 0.84±0.01, 183.3±0.6 vs 200.7±2.1, t=25.108, 20.779, 15.011, all P< 0.05), while the expression of Smad7 decreased (12 w: 0.72 ± 0.02 vs 1.10 ± 0.02, t=30.018, P<0.05). Compared with group D, in group A, atherosclerotic lesions of thoracic aorta were slight, and the expressions of TGF-β1, Smad3 and Col-1 decreased significantly (12 w: 1.05±0.01, 0.81±0.02, 196.3±1.2, t=19.913, 23.377, 11.258, all P<0.05), while the expression of Smad7 increased (12 w: 0.99±0.01, t=21.404, P<0.05). With the extending of gAd intervention, the atherosclerotic lesions mitigated, the expressions of TGF-β1, Smad3 and Col-1 decreased, Smad7 increased significantly (all P<0.05). Conclusions Globular adiponectin may inhibit the TGF-β1/Smads pathway by up-regulating Smad7 or down-regulating TGF-β1 and Smad3, and exert anti-fibrosis action in vascular wall to protect T2DM rats from atherosclerosis. [ABSTRACT FROM AUTHOR]

Purpose: The goal from this in vitro study was to evaluate osteoblast protein expression of collagen type 1 (col 1) and osteopontin (OPN) on titanium surface treated with double etching compared with a zirconia implant surface. Materials and Methods: Discs were selected on both surfaces with respective treatments. Mouse MC3T3-E1 osteoblastic cells were tested for cell viability using the MTT assay. Subsequently, the quantification of col 1 and OPN secreted by osteoblastic cells plated on different surfaces was evaluated by enzyme linked immunosorbent assay (ELISA). Results: Regarding the cell proliferation, statistical analysis showed no significant effect of surface-time interaction and viable cell count on the surfaces of titanium versus zirconia. No statistical differences between the surfaces of titanium and zirconia on cell viability was found. The zirconia surface expression of OPN was significantly higher, which occurred in all times. Furthermore, zirconia demonstrated significantly greater in col 1 expression in 48 and 96 hours compared with titanium. Conclusion: In this study, the zirconia surface demonstrated OPN and col 1 expression significantly higher as compared with titanium. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder caused by disruption of type I collagen synthesis. Previous Brazilian molecular OI studies have been restricted to case reports or small cohorts. The Brazilian OI Network (BOIN) is a multicenter study collecting clinical OI treatment data from five reference centers in three regions of Brazil. To describe the molecular analysis of a large cohort of OI registered at BOIN. Targeted next-generation sequencing (NGS) was performed at a centralized laboratory with the Ion Torrent platform, covering 99.6 % of the coding regions of 18 OI-associated genes. Clinical information was obtained from a clinical database. We included 156 subjects in the molecular analyses. Variants were detected in 121 subjects: 65 (53.7 %) in COL1A1 , 42 (34.7 %) in COL1A2 , 2 (1.7 %) in IFITM5 , one (0.8 %) in CRTAP , three (2.5 %) in P3H1 , two (1.7 %) in PPIB , four (3.3 %) FKBP10 , one (0.8 %) in SERPINH1 , and one (0.8 %) in TMEM38B. Ninety-one distinct variants were identified, of which 26 were novel. Of the 107 variants identified in COL1A1 and COL1A2 , 24.5 % cause mild OI, while the remaining 75.5 % cause moderate, severe, or lethal OI, of which 49.3 % are glycine to serine substitutions. A single variant in FKBP10 (c.179A>C; p.Gln60Pro) was found in three unrelated and non-consanguineous participants living in the same geographic area in Northeast Brazil, suggesting a possible founder effect. Consistent with the literature, 88.4 % of the subjects had a variant in the COL1A1 and COL1A2 genes, with 10 % inherited in an autosomal recessive manner. Notably, one variant in FKBP10 with a potential founder effect requires further investigation. Data from this large cohort improves our understanding of genotype-phenotype correlations for OI in Brazil. • This is the largest molecular analysis study of OI in Brazil. • The majority of cases a collagen I defect was found (88.4 %). • In 9.9 % an autosomal recessive gene play a role in OI. • A possible founder effect was identified in three cases with a variant in FKBP10. [ABSTRACT FROM AUTHOR]

Objective  To evaluate the influence of polymorphisms on genes encoding type I collagen and the genetic susceptibility of tendinopathy. Methodology  Case-control study involving 242 Brazilian athletes from different sports modalities (55 cases of tendinopathy and 187 controls). The polymorphisms COL1A1 (rs1107946) and COL1A2 (rs412777, rs42524, and rs2621215) were analyzed by the TaqMan system. Odds ratio (OR) with their 95% confidence intervals (CIs) were calculated using a nonconditional logistic regression model. Results  The mean age was 24.0 ± 5.6 years old and 65.3% were men. Of the 55 cases of tendinopathy, 25.4% had > 1 affected tendon, the most frequent being patellar (56.3%), rotator cuff (30.9%) and elbow or hand flexors (30.9%). Age and amount of time of sports practice were associated with a higher chance of presenting tendinopathy (5 and 8 times, respectively). The frequency of variant alleles in control and case patients, respectively, was: COL1A1 rs1107946 24.0 and 29.6%; COL1A2 rs412777 36.1 and 27.8%; rs42524 17.5 and 25.9%; and rs2621215 21.3 and 27.8%. After adjusting for confounding factors (age and years of sports practice), COL1A2 rs42524 and rs2621215 polymorphisms were associated with increased risk of tendinopathy (OR = 5.5; 95%CI = 1.2-24.6 and OR = 3.9; IC95% = 1.1-13.5, respectively). The haplotype COL1A2 CGT was associated with low risk for disease development (OR = 0.5; 95%CI = 0.3-0.9). Conclusion  Age (≥ 25 years old), time of sports practice (≥ 6 years) and polymorphisms in the COL1A2 gene increased the risk of developing tendinopathy., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Summary: Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well with the underlying biochemical and molecular abnormalities. Introduction: OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. Methods: The study comprised 85 OI patients aged 45 (19-78) years, Sillence type I ( n = 58), III ( n = 12), and IV ( n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure (quantitative/qualitative defect) by SDS-PAGE was performed in a subset ( n = 67). Results: A qualitative collagen defect predisposed to a more severe phenotype with reduced aBMD, more fractures, and affected anthropometry compared to patients with a quantitative COL-1 defect ( p < 0.05). HRpQCT revealed significant differences between patients with OI type I and IV. Patients with type I had lower vBMD ( p < 0.005), thinner cortexes ( p < 0.001), and reduced trabecular number ( p < 0.005) compared to patients with type IV indicating that HRpQCT may distinguish type I from type IV better than DXA. Conclusion: The defective collagen in patients with OI has pronounced effects on the skeleton. The classical OI types based on the clinical classification show profound differences in bone mass and architecture and the differences correlate well with the underlying biochemical and molecular collagen abnormalities. [ABSTRACT FROM AUTHOR]

Purpose A readily available artificial urinary conduit might be substituted for autologous bowel in standard urinary diversions and minimize bowel associated complications. However, the use of large constructs remains challenging as host cellular ingrowth and/or vascularization is limited. We investigated large, reinforced, collagen based tubular constructs in a urinary diversion porcine model and compared subcutaneously pre-implanted constructs to cell seeded and basic constructs. Materials and Methods Reinforced tubular constructs were prepared from type I collagen and biodegradable Vicryl® meshes through standard freezing, lyophilization and cross-linking techniques. Artificial urinary conduits were created in 17 female Landrace pigs, including 7 with a basic untreated construct, 5 with a construct seeded with autologous urothelial and smooth muscle cells, and 5 with a free graft formed by subcutaneous pre-implantation of a basic construct. All pigs were evaluated after 1 month. Results The survival rate was 94%. At evaluation 1 basic and 1 cell seeded conduit were occluded. Urinary flow was maintained in all conduits created with pre-implanted constructs. Pre-implantation of the basic construct resulted in a vascularized tissue tube, which could be used as a free graft to create an artificial conduit. The outcome was favorable compared to that of the other conduits. Urinary drainage was better, hydroureteronephrosis was limited and tissue regeneration was improved. Conclusions Subcutaneous pre-implantation of a basic reinforced tubular construct resulted in a vascularized autologous tube, which may potentially replace bowel in standard urinary diversions. To our knowledge we introduce a straightforward 2-step procedure to create artificial urinary conduits in a large animal model. [ABSTRACT FROM AUTHOR]