Browsing by Subject "BONE"

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  • Ainola, Mari; Tomaszewski, Waclaw; Ostrowska, Barbara; Wesolowska, Ewa; Wagner, H. Daniel; Swieszkowski, Wojciech; Sillat, Tarvo; Peltola, Emilia; Konttinen, Yrjo T. (2016)
    The aim was to develop a hybrid three-dimensional-tissue engineering construct for chondrogenesis. The hypothesis was that they support chondrogenesis. A biodegradable, highly porous polycaprolactone-grate was produced by solid freeform fabrication. The polycaprolactone support was coated with a chitosan/polyethylene oxide nanofibre sheet produced by electrospinning. Transforming growth factor-3-induced chondrogenesis was followed using the following markers: sex determining region Y/-box 9, runt-related transcription factor 2 and collagen II and X in quantitative real-time polymerase chain reaction, histology and immunostaining. A polycaprolactone-grate and an optimized chitosan/polyethylene oxide nanofibre sheet supported cellular aggregation, chondrogenesis and matrix formation. In tissue engineering constructs, the sheets were seeded first with mesenchymal stem cells and then piled up according to the lasagne principle. The advantages of such a construct are (1) the cells do not need to migrate to the tissue engineering construct and therefore pore size and interconnectivity problems are omitted and (2) the cell-tight nanofibre sheet and collagen-fibre network mimic a cell culture platform for mesenchymal stem cells/chondrocytes (preventing escape) and hinders in-growth of fibroblasts and fibrous scarring (preventing capture). This allows time for the slowly progressing, multiphase true cartilage regeneration.
  • Kyöstilä, Kaisa; Syrjä, Pernilla; Lappalainen, Anu K.; Arumilli, Meharji; Hundi, Sruthi; Karkamo, Veera; Viitmaa, Ranno; Hytönen, Marjo K.; Lohi, Hannes (2019)
    Inherited skeletal disorders affect both humans and animals. In the current study, we have performed series of clinical, pathological and genetic examinations to characterize a previously unreported skeletal disease in the Karelian Bear Dog (KBD) breed. The disease was recognized in seven KBD puppies with a variable presentation of skeletal hypomineralization, growth retardation, seizures and movement difficulties. Exome sequencing of one affected dog revealed a homozygous missense variant (c. 1301T > G; p. V434G) in the tissue non-specific alkaline phosphatase gene, ALPL. The identified recessive variant showed full segregation with the disease in a cohort of 509 KBDs with a carrier frequency of 0.17 and was absent from 303 dogs from control breeds. In humans, recessive and dominant ALPL mutations cause hypophosphatasia (HPP), a metabolic bone disease with highly heterogeneous clinical manifestations, ranging from lethal perinatal hypomineralization to a relatively mild dental disease. Our study reports the first naturally occurring HPP in animals, resembling the human infantile form. The canine HPP model may serve as a preclinical model while a genetic test will assist in breeding programs.
  • Kaila-Kangas, Leena; Koskinen, Aki; Leino-Arjas, Päivi; Virtanen, Marianna; Härkänen, Tommi; Lallukka, Tea (2018)
    Background: Previous studies have not distinguished between different alcohol-use histories, which could have contributed to the current inconsistent evidence regarding the relationship between alcohol use and subsequent sickness absence. We thus examined alcohol use and subsequent diagnosis-specific sickness absence in groups with different levels of alcohol use, as well as in lifelong abstainers, former drinkers, and people with clinical alcohol use disorders. Methods: The data of the population-based Health 2000 Survey (BRIF8901) of 3666 Finns aged 30-55 were linked with national registers on medically certified sickness absences lasting for > 10 working days (long-term) for all causes (2000 -2010) and for mental or musculoskeletal disorders (2004-2010), as well as with registers on pensions and death (2000-2010). Alcohol use was assessed by questionnaire. Chronic somatic diseases were evaluated at baseline in a clinical examination, and common mental and alcohol use disorders using the Composite International Diagnostic Interview (CIDI). Cox regression analyses were conducted with censoring for death and retirement from work. Results: During an average 10-year follow-up, 56.0% of the participants had at least one long-term sickness absence period. Compared with light drinkers, those having an alcohol use disorder had increased risk of all-cause sickness absence (HR = 1.27; 95% CI = 1.04 - 1.54) and sickness absence due to mental disorders (HR = 2.16; 95% CI = 1.39 - 3.35), when somatic and mental disorders as well as demographic, lifestyle-related and occupational factors at baseline were accounted for. Lifelong abstainers did not differ from light drinkers. Also high-volume drinking (HR = 1.52; 95% CI 1.03 - 2.25) and former drinking (HR = 1.57; 95% CI = 1.15 - 2.15) were associated with long-term sickness absence due to mental disorders. Alcohol use was not predictive of sickness absence due to musculoskeletal disorders. Conclusions: These results highlight the need to distinguish between former drinking and lifelong abstinence, as only former drinking was associated with sickness absence. Alcohol use disorder and high-volume drinking were strongly predictive of sickness absence due to mental disorders. Identifying people with excessive alcohol use e.g. in occupational health care, and mapping and supporting their mental health may help in preventing sickness absences.
  • Purisha, Zenith; Karhula, Sakari S.; Ketola, Juuso H.; Rimpeläinen, Juho; Nieminen, Miika T.; Saarakkala, Simo; Kröger, Heikki; Siltanen, Samuli (2019)
    X-ray tomography is a reliable tool for determining the inner structure of 3-D object with penetrating X-rays. However, traditional reconstruction methods, such as Feldkamp-Davis-Kress (FDK), require dense angular sampling in the data acquisition phase leading to long measurement times, especially in X-ray micro-tomography to obtain high-resolution scans. Acquiring less data using greater angular steps is an obvious way for speeding up the process and avoiding the need to save huge data sets. However, computing 3-D reconstruction from such a sparsely sampled data set is difficult because the measurement data are usually contaminated by errors, and linear measurement models do not contain sufficient information to solve the problem in practice. An automatic regularization method is proposed for robust reconstruction, based on enforcing sparsity in the 3-D shearlet transform domain. The inputs of the algorithm are the projection data and a priori known expected degree of sparsity, denoted as 0 <C-pr
  • Mustonen, Anne-Mari; Käkelä, Reijo; Finnilä, Mikko A. J.; Sawatsky, Andrew; Korhonen, Rami K.; Saarakkala, Simo; Herzog, Walter; Paakkonen, Tommi; Nieminen, Petteri (2019)
    The infrapatellar fat pad (IFP) of the knee joint has received lots of attention recently due to its emerging role in the pathogenesis of osteoarthritis (OA), where it displays an inflammatory phenotype. The aim of the present study was to examine the infrapatellar fatty acid (FA) composition in a rabbit (Oryctolagus cuniculus) model of early OA created by anterior cruciate ligament transection (ACLT).
  • Mäkitie, Riikka E.; Kämpe, Anders; Costantini, Alice; Alm, Jessica J.; Magnusson, Per; Mäkitie, Outi (2020)
    Recent advancements in genetic research have uncovered new forms of monogenic osteoporosis, expanding our understanding of the molecular pathways regulating bone health. Despite active research, knowledge on the pathomechanisms, disease-specific biomarkers, and optimal treatment in these disorders is still limited. Mutations in WNT1, encoding a WNT/beta-catenin pathway ligand WNT1, and PLS3, encoding X chromosomally inherited plastin 3 (PLS3), both result in early-onset osteoporosis with prevalent fractures and disrupted bone metabolism. However, despite marked skeletal pathology, conventional bone markers are usually normal in both diseases. Our study aimed to identify novel bone markers in PLS3 and WNT1 osteoporosis that could offer diagnostic potential and shed light on the mechanisms behind these skeletal pathologies. We measured several parameters of bone metabolism, including serum dickkopf-1 (DKK1), sclerostin, and intact and C-terminal fibroblast growth factor 23 (FGF23) concentrations in 17 WNT1 and 14 PLS3 mutation-positive subjects. Findings were compared with 34 healthy mutation-negative subjects from the same families. Results confirmed normal concentrations of conventional metabolic bone markers in both groups. DKK1 concentrations were significantly elevated in PLS3 mutation-positive subjects compared with WNT1 mutation-positive subjects (p <.001) or the mutation-negative subjects (p = .002). Similar differences were not seen in WNT1 subjects. Sclerostin concentrations did not differ between any groups. Both intact and C-terminal FGF23 were significantly elevated in WNT1 mutation-positive subjects (p = .039 and p = .027, respectively) and normal in PLS3 subjects. Our results indicate a link between PLS3 and DKK1 and WNT1 and FGF23 in bone metabolism. The normal sclerostin and DKK1 levels in patients with impaired WNT signaling suggest another parallel regulatory mechanism. These findings provide novel information on the molecular networks in bone. Extended studies are needed to investigate whether these biomarkers offer diagnostic value or potential as treatment targets in osteoporosis. (c) 2020 American Society for Bone and Mineral Research.
  • Orosz, Zsuzsanna Z.; Bardos, Helga; Shemirani, Amir H.; Debreceni, Ildiko Beke; Lassila, Riitta; Riikonen, Antti S.; Hovinga, Johanna A. Kremer; Seiler, Theo G.; van Dorland, Hendrika A.; Schroeder, Verena; Boda, Zoltan; Nemes, Laszlo; Frueh Eppstein, Beatrice; Nagy, Bence; Facsko, Andrea; Kappelmayer, Janos; Muszbek, Laszlo (2019)
    Cellular factor XIII (cFXIII, FXIII-A(2)), a transglutaminase, has been demonstrated in a few cell types. Its main function is to cross-link proteins by isopeptide bonds. Here, we investigated the presence of cFXIII in cells of human cornea. Tissue sections of the cornea were immunostained for FXIII-A in combination with staining for CD34 antigen or isopeptide cross-links. Isolated corneal keratocytes were also evaluated by immunofluorescent microscopy and flow cytometry. FXIII-A in the corneal stroma was quantified by Western blotting. FXIII-A mRNA was detected by RT-qPCR. The cornea of FXIII-A-deficient patients was evaluated by cornea topography. FXIII-A was detected in 68 +/- 13% of CD34+ keratocytes. Their distribution in the corneal stroma was unequal; they were most abundant in the subepithelial tertile. cFXIII was of cytoplasmic localization. In the stroma, 3.64 ng cFXIII/mg protein was measured. The synthesis of cFXIII by keratocytes was confirmed by RT-qPCR. Isopeptide cross-links were detected above, but not within the corneal stroma. Slight abnormality of the cornea was detected in six out of nine FXIII-A-deficient patients. The presence of cFXIII in human keratocytes was established for the first time. cFXIII might be involved in maintaining the stability of the cornea and in the corneal wound healing process.
  • Tantiyavarong, Pichaya; Kramer, Anneke; Heaf, James G.; Finne, Patrik; Asberg, Anders; Cases, Aleix; Caskey, Fergus J.; Massy, Ziad A.; Jager, Kitty J.; Noordzij, Marlies (2020)
    Background. Kidney transplantation should improve abnormalities that are common during dialysis treatment, like anaemia and mineral and bone disorder. However, its impact is incompletely understood. We therefore aimed to assess changes in clinical indicators after the transition from chronic dialysis to kidney transplantation. Methods. We used European Renal Association-European Dialysis and Transplant Association Registry data and included adult dialysis patients for whom data on clinical indicators before and after transplantation (2005-15) were available. Linear mixed models were used to quantify the effect of transplantation and of time after transplantation for each indicator. Results. In total, 16 312 patients were included. The mean age at transplantation was 50.1 (standard deviation 14.2) years, 62.9% were male and 70.2% were on haemodialysis before transplantation. Total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides increased right after transplantation but decreased thereafter. All other indicators normalized or approached the target range soon after transplantation and these improvements were sustained for the first 4 years of follow-up. In patients with higher estimated glomerular filtration rate (eGFR) levels (30-60 and >60 mL/min/1.73 m(2)), the improvement of haemoglobin, ferritin, ionized calcium, phosphate, parathyroid hormone, HDL cholesterol, triglycerides, albumin and C-reactive protein levels was more pronounced than in patients with a lower eGFR ( Conclusions. Except for total cholesterol, LDL cholesterol and triglycerides, all clinical indicators improved after transplantation. These improvements were related to eGFR. Nevertheless, values remained out of range in a considerable proportion of patients and anaemia and hyperparathyroidism were still common problems. Further research is needed to understand the complex relationship between eGFR and the different clinical indicators.
  • Cavalli, Emma; Levinson, Clara; Hertl, Matthias; Broguiere, Nicolas; Brück, Oscar; Mustjoki, Satu; Gerstenberg, Anja; Weber, Daniel; Salzmann, Gian; Steinwachs, Matthias; Barreto, Goncalo; Zenobi-Wong, Marcy (2019)
    Treating cartilage injuries and degenerations represents an open surgical challenge. The recent advances in cell therapies have raised the need for a potent off-the-shelf cell source. Intra-articular injections of TGF-beta transduced polydactyly chondrocytes have been proposed as a chronic osteoarthritis treatment but despite promising results, the use of gene therapy still raises safety concerns. In this study, we characterized infant, polydactyly chondrocytes during in vitro expansion and chondrogenic redifferentiation. Polydactyly chondrocytes have a steady proliferative rate and re-differentiate in 3D pellet culture after up to five passages. Additionally, we demonstrated that polydactyly chondrocytes produce cartilage-like matrix in a hyaluronan-based hydrogel, namely transglutaminase cross-linked hyaluronic acid (HA-TG). We utilized the versatility of TG cross-linking to augment the hydrogels with heparin moieties. The heparin chains allowed us to load the scaffolds with TGF-beta 1 which induced cartilage-like matrix deposition both in vitro and in vivo in a subcutaneous mouse model. This strategy introduces the possibility to use infant, polydactyly chondrocytes for the clinical treatment of joint diseases.
  • Escudier, Bernard; Sharma, Padmanee; McDermott, David F.; George, Saby; Hammers, Hans J.; Srinivas, Sandhya; Tykodi, Scott S.; Sosman, Jeffrey A.; Procopio, Giuseppe; Plimack, Elizabeth R.; Castellano, Daniel; Gurney, Howard; Donskov, Frede; Peltola, Katriina; Wagstaff, John; Gauler, Thomas C.; Ueda, Takeshi; Zhao, Huanyu; Waxman, Ian M.; Motzer, Robert J.; CheckMate 025 Investigators (2017)
    Background: The randomized, phase 3 CheckMate 025 study of nivolumab (n = 410) versus everolimus (n = 411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). Objective: To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Design, setting, and participants: Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Intervention: Nivolumab 3 mg/kg every 2 wk or everolimus 10 mg once daily. Results and limitations: The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and >= 65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32-0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. Conclusion: The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Laitinen, M. K.; Stevenson, J. D.; Evans, S.; Abudu, A.; Sumathi, V.; Jeys, L. M.; Parry, M. C. (2019)
    Introduction Chondroblastoma is a rare benign bone tumour that usually occurs in children and young adults. They are cartilaginous tumours arising in the epiphysis or apophysis of a long bone. The tumour is classified as benign, although rare cases of pulmonary metastases have been reported. The aims of this study were to describe clinical, radiographic characteristics of chondroblastoma; to analyse the local recurrence rate and complications associated with surgery. Material and methods This retrospective study included 177 patients, who had been diagnosed with a chondroblastoma in extremity between 1990 and 2015. Results The most common site was proximal tibia 20%, followed by proximal humerus 19%, proximal femur 18%, distal femur 16% and foot 15%. One patient has died of the disease and one patient is alive after being operated for lung metastases. There was local recurrence in 25/177 (14%) patients. The median time to local recurrence was 10 months (range 3-158 months). The most common site for local recurrence was proximal tibia (22.2%). The proximal femur was the location in 32/178 (18%) of the cases. 18/32 (56%) were in the greater trochanter and 14/32 (44%) in the femoral head. The mean age was lower in tumours located in femoral head when compared to the greater trochanter; 19.5 years and 13.9 years respectively (p=0.004). Tumours located in greater trochanter were all curetted without further complications. Local recurrence was seen more often in femoral head tumours, though without statistical significance; 3/14 (21%) and none, respectively (p=0.073). Conclusions Chondroblastoma is a rare benign to intermediate grade bone tumour with a potential to metastasise. Femoral head chondroblastoma is rare, presenting 4.5% of all chondroblastoma cases. Around 50% of the chondroblastoma in femoral head. occur in patients with open growth plates.
  • Vento, Seija Inkeri; Vähämurto, Pauli; Silventoinen, Kaija; Karjalainen-Lindsberg, Marja-Liisa; Mannisto, Susanna; Leppa, Sirpa; Makitie, Antti Aarni (2017)
    Objectives: Extramedullary plasmacytoma in the sinonasal tract or nasopharynx is rare. The aim of the study was to review data on symptoms, clinical findings, treatment and follow-up of plasmacytomas in the sinonasal and nasopharyngeal regions in order to delineate the main clinical characteristics and the optimal management. Method: Twenty-five patients with sinonasal or nasopharyngeal plasmacytoma, diagnosed and treated at the Helsinki University Hospital during a 39-year period from 1975 to 2013 were retrospectively reviewed. Results: There were 18 males and 7 females with a median age of 66 years (range, 36-80). Sixty-eight percent received only radiotherapy or (chemo)radiotherapy. Forty-seven percent of them had a complete response to primary radiotherapy and one patient had a complete response after receiving additional brachytherapy. Four patients were treated primarily with surgery only. Two of them had a local recurrence, but were then successfully treated with radiotherapy. Altogether, four patients received a combination of surgery and (chemo)radiotherapy. Forty-four percent were alive with no evidence of disease after a median follow-up time of 78 months. Forty percent died of their disease and 16% died of other causes. Conclusions: Our study supports radiotherapy as a treatment of choice, but for small tumours surgery alone or in combination with radiotherapy may also be considered. Chinese abstract
  • Erkman, Ahmet Cem; Basoglu, Oksan; Basibuyuk, Gulusan Ozgun; Kirmizioglu, Pinar Gozluk; Yigit, Ayhan; Yalcin, Yarenkur Alkan; Kaya, Ferhat (2016)
    The excavations conducted at Van Castle Mound, East Anatolia, between 1987 and 2010 uncovered a total of 328 human skeletons dating back to the Medieval period. Thirty trauma cases were identified within the collection, constituting 9.14% of the entire population. Typology and distribution of the trauma among different sexes indicated that depression fractures, oblique fractures, comminuted fractures, and head deformation were more frequently observed in male skeletons, while a post-fractural infection appeared only in a female skeleton. Trauma cases were more common on post-cranial bones. In addition, a trepanned cranial specimen belonging to a mature individual is identified in which grooving technique was performed. Most of the observed trauma cases were related to heavy labor, unsafe working conditions, and challenges of everyday agrarian life. Previous paleopathological studies from the Medieval Van Castle Mound also indicates an insufficient nutritation and high physical stress.
  • Knowler, Susan P.; Kiviranta, Anna-Mariam; McFadyen, Angus K.; Jokinen, Tarja S.; La Ragione, Roberto M.; Rusbridge, Clare (2017)
    Objectives To characterize and compare the phenotypic variables of the hindbrain and craniocervical junction associated with syringomyelia (SM) in the Chihuahua, Affenpinscher and Cavalier King Charles Spaniel (CKCS). Method Analysis of 273 T1-weighted mid-sagittal DICOM sequences of the hindbrain and craniocer-vical junction from 99 Chihuahuas, 42 Affenpinschers and 132 CKCSs. The study compared 22 morphometric features (11 lines, eight angles and three ratios) of dogs with and without SM using refined techniques based on previous studies of the Griffon Bruxellois (GB) using Discriminant Function Analysis and ANOVA with post-hoc corrections. Results The analysis identified 14/22 significant traits for SM in the three dog breeds, five of which were identical to those reported for the GB and suggest inclusion of a common aetiology. One ratio, caudal fossa height to the length of the skull base extended to an imaginary point of alignment between the atlas and supraoccipital bones, was common to all three breeds (p values 0.029 to <0.001). Associated with SM were a reduced occipital crest and two acute changes in angulation i) 'sphenoid flexure' at the spheno-occipital synchondrosis ii) 'cervical flexure' at the foramen magnum allied with medulla oblongata elevation. Comparing dogs with and without SM, each breed had a unique trait: Chihuahua had a smaller angle between the dens, atlas and basioccipital bone (p value <0.001); Affenpinschers had a smaller dis-tance from atlas to dens (p value 0.009); CKCS had a shorter distance between the spheno-occipital synchondrosis and atlas (p value 0.007). Conclusion The selected morphometries successfully characterised conformational changes in the brain and craniocervical junction that might form the basis of a diagnostic tool for all breeds. The severity of SM involved a spectrum of abnormalities, incurred by changes in both angulation and size that could alter neural parenchyma compliance and/or impede cerebrospinal fluid channels.
  • Salonius, Eve; Rieppo, Lassi; Nissi, Mikko J.; Pulkkinen, Hertta J.; Brommer, Harold; Bruenott, Anne; Silvast, Tuomo S.; Van Weeren, P. Rene; Muhonen, Virpi; Brama, Pieter A. J.; Kiviranta, Ilkka (2019)
    Aim: The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Material and Methods: Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, with MR and mu CT imaging, polarized light microscopy, standard histology, and immunohistochemistry at 12 months. Results: Filling of 2 mm chondral defects was good (77.8 +/- 8.5%), but proteoglycan depletion was evident in Safranin-O staining and gadolinium-enhanced MRI (T-1Gd). Larger chondral defects showed poor filling (50.6 +/- 2.7% in 4 mm and 31.9 +/- 7.3% in 8 mm defects). Lesion filling in 2, 4, and 8 mm osteochondral defects was 82.3 +/- 3.0%, 68.0 +/- 4.6% and 70.8 +/- 15.4%, respectively. Type II collagen staining was seen in 9/15 osteochondral defects but only in 1/15 chondral defects. Subchondral bone pathologies were evident in 14/15 osteochondral samples but only in 5/15 chondral samples. Although osteochondral lesions showed better neotissue quality than chondral lesions, the overall repair was deemed unsatisfactory because of the subchondral bone pathologies. Conclusion: We recommend classifying 4 mm as critical osteochondral lesion size and 2 mm as critical chondral lesion size for cartilage repair research in the equine carpal joint model.
  • Akmal, Jan Sher; Salmi, Mika; Hemming, Björn; Teir, Linus; Suomalainen, Anni; Kortesniemi, Mika; Partanen, Jouni; Lassila, Antti (2020)
    Featured Application Accuracy of additively manufactured implants for clinical surgery. Abstract In craniomaxillofacial surgical procedures, an emerging practice adopts the preoperative virtual planning that uses medical imaging (computed tomography), 3D thresholding (segmentation), 3D modeling (digital design), and additive manufacturing (3D printing) for the procurement of an end-use implant. The objective of this case study was to evaluate the cumulative spatial inaccuracies arising from each step of the process chain when various computed tomography protocols and thresholding values were independently changed. A custom-made quality assurance instrument (Phantom) was used to evaluate the medical imaging error. A sus domesticus (domestic pig) head was analyzed to determine the 3D thresholding error. The 3D modeling error was estimated from the computer-aided design software. Finally, the end-use implant was used to evaluate the additive manufacturing error. The results were verified using accurate measurement instruments and techniques. A worst-case cumulative error of 1.7 mm (3.0%) was estimated for one boundary condition and 2.3 mm (4.1%) for two boundary conditions considering the maximum length (56.9 mm) of the end-use implant. Uncertainty from the clinical imaging to the end-use implant was 0.8 mm (1.4%). This study helps practitioners establish and corroborate surgical practices that are within the bounds of an appropriate accuracy for clinical treatment and restoration.
  • Lehtovirta, S.; Mäkitie, R. E.; Casula, V.; Haapea, M.; Niinimäki, J.; Niinimäki, T.; Peuna, A.; Lammentausta, E.; Mäkitie, O.; Nieminen, M.T. (2019)
    Objective: WNT signaling is of key importance in chondrogenesis and defective WNT signaling may contribute to the pathogenesis of osteoarthritis and other cartilage diseases. Biochemical composition of articular cartilage in patients with aberrant WNT signaling has not been studied. Our objective was to assess the knee articular cartilage in WNT1 mutation-positive individuals using a 3.0T MRI unit to measure cartilage thickness, relaxation times, and texture features. Design: Cohort comprised mutation-positive (N = 13; age 17-76 years) and mutation-negative (N = 13; 16-77 years) subjects from two Finnish families with autosomal dominant WNT1 osteoporosis due to a heterozygous missense mutation c.652T>G (p.C218G) in WNT1. All subjects were imaged with a 3.0T MRI unit and assessed for cartilage thickness, T2 and T1 rho relaxation times, and T2 texture features contrast, dissimilarity and homogeneity of T2 relaxation time maps in six regions of interest (ROIs) in the tibiofemoral cartilage. Results: All three texture features showed opposing trends with age between the groups in the medial tibiofemoral cartilage (P = 0.020-0.085 for the difference of the regression coefficients), the mutation-positive individuals showing signs of cartilage preservation. No significant differences were observed in the lateral tibiofemoral cartilage. Cartilage thickness and means of T2 relaxation time did not differ between groups. Means of T1r relaxation time were significantly different in one ROI but the regression analysis displayed no differences. Conclusions: Our results show less age-related cartilage deterioration in the WNT1 mutation-positive than the mutation-negative subjects. This suggests, that the WNT1 mutation may alter cartilage turnover and even have a potential cartilage-preserving effect. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
  • Murshid, S. A.; Takano-Yamamoto, T.; Kamioka, H. (2018)
    Objectives: The transition from osteoblasts to osteocytes is associated with dramatic changes in the cytoskeleton. We previously showed that the formation of osteoblast cell processes in 3D culture is microtubule dependent. However, the distribution of microtubules during the transition from osteoblasts to osteocytes in vivo is unknown. In this study, we investigated the distribution of microtubules in osteocytes in vivo. Methods: We observed the microtubules in osteocytes in chick embryonic calvaria via fluorescence staining of microtubules and confocal laser scanning microscopy. Results: Microtubules were observed throughout the cytoplasm in all examined osteoblasts. In immature osteocytes, several cell processes contained microtubules, whereas in mature osteocytes, microtubules were localized only in the cell body. Conclusion: These results suggest that the early arrangement of microtubules may be correlated with the initial development of osteocyte processes. (C) 2018 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.
  • Karhula, Sakari S.; Finnilä, Mikko A.; Lammi, Mikko J.; Ylärinne, Janne H.; Kauppinen, Sami; Rieppo, Lassi; Pritzker, Kenneth P. H.; Nieminen, Heikki J.; Saarakkala, Simo (2017)
    Contrast-enhanced micro-computed tomography (CE mu CT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CE mu CT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0-13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13- 39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CE mu CT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CE mu CT method for 3D characterization of articular cartilage.
  • Munukka, M.; Waller, B.; Rantalainen, T.; Hakkinen, A.; Nieminen, M. T.; Lammentausta, E.; Kujala, U. M.; Paloneva, J.; Sipila, S.; Peuna, A.; Kautiainen, H.; Selanne, H.; Kiviranta, I.; Heinonen, A. (2016)
    Objective: To study the efficacy of aquatic resistance training on biochemical composition of tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis (OA). Design: Eighty seven volunteer postmenopausal women, aged 60-68 years, with mild knee OA (Kellgren-Lawrence grades I/II and knee pain) were recruited and randomly assigned to an intervention (n = 43) and control (n = 44) group. The intervention group participated in 48 supervised aquatic resistance training sessions over 16 weeks while the control group maintained usual level of physical activity. The biochemical composition of the medial and lateral tibiofemoral cartilage was estimated using single-slice transverse relaxation time (T2) mapping and delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC index). Secondary outcomes were cardiorespiratory fitness, isometric knee extension and flexion force and knee injury and OA outcome (KOOS) questionnaire. Results: After 4-months aquatic training, there was a significant decrease in both T2 -1.2 ms (95% confidence interval (CI): -2.3 to -0.1, P = 0.021) and dGEMRIC index -23 ms (-43 to -3, P = 0.016) in the training group compared to controls in the full thickness posterior region of interest (ROI) of the medial femoral cartilage. Cardiorespiratory fitness significantly improved in the intervention group by 9.8% (P = 0.010). Conclusions: Our results suggest that, in postmenopausal women with mild knee OA, the integrity of the collagen-interstitial water environment (T2) of the tibiofemoral cartilage may be responsive to low shear and compressive forces during aquatic resistance training. More research is required to understand the exact nature of acute responses in dGEMRIC index to this type of loading. Further, aquatic resistance training improves cardiorespiratory fitness. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.