Browsing by Subject "OSTEOARTHRITIS"

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  • Nieminen, H. J.; Gahunia, H. K.; Pritzker, K. P. H.; Ylitalo, T.; Rieppo, L.; Karhula, S. S.; Lehenkari, P.; Haeggstörm, E.; Saarakkala, S. (2017)
    Objective: Histopathological grading of osteochondral (OC) tissue is widely used in osteoarthritis (OA) research, and it is relatively common in post-surgery in vitro diagnostics. However, relying on thin tissue section, this approach includes a number of limitations, such as: (1) destructiveness, (2) sample processing artefacts, (3 ) 2D section does not represent spatial 3D structure and composition of the tissue, and (4) the final outcome is subjective. To overcome these limitations, we recently developed a contrast-enhanced mu CT (CE mu CT) imaging technique to visualize the collagenous extracellular matrix (ECM) of articular cartilage (AC). In the present study, we demonstrate that histopathological scoring of OC tissue from CE mu CT is feasible. Moreover, we establish a new, semi-quantitative OA mu CT grading system for OC tissue. Results: Pathological features were clearly visualized in AC and subchondral bone (SB) with mu CT and verified with histology, as demonstrated with image atlases. Comparison of histopathological grades (OARSI or severity (0-3)) across the characterization approaches, CE mu CT and histology, excellent (0.92, 95% CI = [0.84, 0.96], n = 30) or fair (0.50, 95% CI = [0.16, 0.74], n = 27) intra-class correlations (ICC), respectively. A new mu CT grading system was successfully established which achieved an excellent cross-method (mu CT vs histology) reader-to-reader intra-class correlation (0.78, 95% CI = [0.58, 0.89], n = 27). Conclusions: We demonstrated that histopathological information relevant to OA can reliably be obtained from CE mu CT images. This new grading system could be used as a reference for 3D imaging and analysis techniques intended for volumetric evaluation of OA pathology in research and clinical applications. (C) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
  • Kauppinen, S.; Karhula, S. S.; Thevenot, J.; Ylitalo, T.; Rieppo, L.; Kestilä, I.; Haapea, M.; Hadjab, I.; Finnilä, M. A.; Quenneville, E.; Garon, M.; Gahunia, H. K.; Pritzker, K. P. H.; Buschmann, M. D.; Saarakkala, S.; Nieminen, H. J. (2019)
    Objective: Our aim is to establish methods for quantifying morphometric properties of calcified cartilage (CC) from micro-computed tomography (mu CT). Furthermore, we evaluated the feasibility of these methods in investigating relationships between osteoarthritis (OA), tidemark surface morphology and open subchondral channels (OSCCs). Method: Samples (n = 15) used in this study were harvested from human lateral tibial plateau (n = 8). Conventional roughness and parameters assessing local 3-dimensional (3D) surface variations were used to quantify the surface morphology of the CC. Subchondral channel properties (percentage, density, size) were also calculated. As a reference, histological sections were evaluated using Histopathological osteoarthritis grading (OARSI) and thickness of CC and subchondral bone (SCB) was quantified. Results: OARSI grade correlated with a decrease in local 3D variations of the tidemark surface (amount of different surface patterns (r(s) = -0.600, P = 0.018), entropy of patterns (EP) (r(s) = -0.648, P = 0.018), homogeneity index (HI) (r(s) = 0.555, P = 0.032)) and tidemark roughness (TMR) (r(s) = -0.579, P = 0.024). Amount of different patterns (ADP) and EP associated with channel area fraction (CAF) (r(p) = 0.876, P <0.0001; r(p) = 0.665, P = 0.007, respectively) and channel density (CD) (r(p) = 0.680, P = 0.011; r(p) = 0.582, P = 0.023, respectively). TMR was associated with CAF (r(p) = 0.926, P <0.0001) and average channel size (r(p) = 0.574, P = 0.025). CC topography differed statistically significantly in early OA vs healthy samples. Conclusion: We introduced a mu-CT image method to quantify 3D CC topography and perforations through CC. CC topography was associated with OARSI grade and OSCC properties; this suggests that the established methods can detect topographical changes in tidemark and CC perforations associated with OA. (c) 2018 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (
  • Järvinen, Teppo N. L.; Sihvonen, Raine; Englund, Martin (2014)
  • Lankinen, Petteri; Laasik, Raul; Kivimäki, Mika; Aalto, Ville; Saltychev, Mikhail; Vahtera, Jussi; Mäkelä, Keijo (2019)
    Background: Osteoarthritis is one of the leading causes of disability in working-age patients. The total number of working-age patients undergoing total-knee arthroplasty (TKA) is continuously increasing. The purpose of this study was to identify predictive factors related to general health, health risk behaviors and socioeconomic status influencing the rate of return to work after a TKA. Methods: Overall there were 151,901 patients included in the Finnish Public Sector (FPS) study. The response rate varied between 65 and 73% during the study period. We used Cox proportional hazard models to examine patient-related predictive factors that may influence the rate of return to work after TKA in a cohort of patients (n = 452; n = 362 female; mean age 56.4 years). Predictive factors were measured on average 3.6 years before the operation. Results: Of the patients, 87% returned to work within one year after TKA at a mean of 116 calendar days. In multivariate analysis, patients at sick-leave 30 days of sick-leave. Compared with patients in manual work, those in higher or lower level non-manual work showed a 2.6-fold (1.95-3.52) and 1.5-fold (1.15-1.92) increased probability of returning to work. Age, sex, health risk behaviors, obesity, physical comorbidities, common mental disorders, and other studied health-related factors were not associated with the rate of return to work. Conclusions: Non-manual job, good self-rated general health and preoperative sick leave
  • Järvinen, Teppo L. N.; Sihvonen, Raine; Englund, Martin (2014)
  • Makela, Keijo T.; Visuri, Tuomo; Pulkkinen, Pekka; Eskelinen, Antti; Remes, Ville; Virolainen, Petri; Junnila, Mika; Pukkala, Eero (2014)
  • Nuutinen, Timo K.; Madanat, R.; Både, K. W.; Ristolainen, L. H.; Kauppinen, H.; Manninen, M. J. (2023)
    Purpose Treatment of secondary knee osteoarthritis with a significant extra-articular deformity can be challenging. In such cases, an osteotomy or a custom-made hinged knee arthroplasy (CMH) are treatment options. However, there are limited data on the outcomes of using CMHs. Thus, the aim of this retrospective study was to assess the clinical results and subjective outcomes of CMHs. Methods We reviewed 9 CMHs (Endo-Model, LINK) in 7 patients with a minimum of 2-year follow-up. Upon the last follow-up, we evaluated MA, stability and range of movement (ROM). Oxford Knee Score (OKS) was used to evaluate patient-reported outcomes. Results The average age upon surgery was 61 years (48-76 years), and the follow-up period was 66 months. There were no early complications. Two CMHs were revised, one due to aseptic loosening and one due to late-onset haematogenic infection. Pre-operatively, MA varied from 18 degrees (average 11 degrees) valgus-deformity to 30 degrees (average 17 degrees) varus-deformity. Post-operatively, 7/9 (78%) of patients achieved better MA. Upon follow-up, the average OKS was 41/48, and ROM was 113 degrees. Conclusions Patients treated with CMHs achieved good clinical and patient-reported outcomes. There were no early reoperations, and revision rate was relatively low. Overall, CMH could be considered for low-demand patients with increased operative risks.
  • Nieminen, Heikki J.; Ylitalo, Tuomo; Suuronen, Jussi-Petteri; Rahunen, Krista; Salmi, Ari; Saarakkala, Simo; Serimaa, Ritva; Haeggstrom, Edward (2015)
    There is no cure for osteoarthritis. Current drug delivery relies on systemic delivery or injections into the joint. Because articular cartilage (AC) degeneration can be local and drug exposure outside the lesion can cause adverse effects, localized drug delivery could permit new drug treatment strategies. We investigated whether intense megahertz ultrasound (frequency: 1.138 MHz, peak positive pressure: 2.7 MPa, I-spta: 5 W/cm(2), beam width: 5.7 mm at -6 dB, duty cycle: 5%, pulse repetition frequency: 285 Hz, mechanical index: 1.1) can deliver agents into AC without damaging it. Using ultrasound, we delivered a drug surrogate down to a depth corresponding to 53% depth of the AC thickness without causing histologically detectable damage to the AC. This may be important because early osteoarthritis typically exhibits histopathologic changes in the superficial AC. In conclusion, we identify intense megahertz ultrasound as a technique that potentially enables localized non-destructive delivery of osteoarthritis drugs or drug carriers into articular cartilage. (E-mail: (C) 2015 World Federation for Ultrasound in Medicine & Biology.
  • Pérez, Alejandro Garcia; Nieminen, Heikki J.; Finnilä, Mikko; Salmi, Ari; Pritzker, Kenneth P. H.; Lampsijärvi, Eetu; Paulin, Tor; Airaksinen, Anu J.; Saarakkala, Simo; Haeggström, Edward (2018)
    Localized delivery of drugs into articular cartilage (AC) may facilitate the development of novel therapies to treat osteoarthritis (OA). We investigated the potential of spark-gap-generated sound to deliver a drug surrogate, i.e., methylene blue (MB), into AC. In vitro experiments exposed bovine AC samples to either simultaneous sonication and immersion in MB (Treatment 1; n = 10), immersion in MB after sonication (Control 1; n = 10), solely immersion in MB (Control 2; n = 10), or neither sonication nor immersion in MB (Control 3; n = 10). The sonication protocol consisted of 1,000 spark-gap -generated pulses. Delivery of MB into AC was estimated from optical absorbance in transmission light microscopy. Optical absorbance was significantly greater in the treatment group up to 900 mu m depth from AC surface as compared to all controls. Field emission scanning electron microscopy (FESEM), histological analysis, and digital densitometry (DD) of sonicated (n = 6) and non-sonicated (n = 6) samples showed no evidence of sonication-induced changes in proteoglycan content or collagen structure. Consequently, spark-gap -generated sound may offer a solution for localized drug delivery into AC in a non-destructive fashion. Further research on this method may contribute to OA drug therapies.
  • Hyytiäinen, Heli K.; Mölsä, Sari H.; Junnila, Jouni J. T.; Laitinen-Vapaavuori, Outi M.; Hielm-Björkman, Anna K. (2018)
    This study aimed at developing a quantitative testing battery for dogs' stifle functionality, as, unlike in human medicine, currently none is available in the veterinary field. Forty-three dogs with surgically treated unilateral cranial cruciate ligament rupture and 21 dogs with no known musculoskeletal problems were included. Eight previously studied tests: compensation in sitting and lying positions, symmetry of thrust in hindlimbs when rising from lying and sitting, static weight bearing, stifle flexion and extension and muscle mass symmetry, were summed into the Finnish Canine Stifle Index (FCSI). Sensitivities and specificities of the dichotomised FCSI score were calculated against orthopaedic examination, radiological and force platform analysis and a conclusive assessment (combination of previous). One-way analysis of variance (ANOVA)was used to evaluate FCSI score differences between the groups. Cronbach's alpha for internal consistency was calculated. The range of the index score was 0-263, with a proposed cut-off value of 60 between 'adequate' and 'compromised' functional performance. In comparison to the conclusive assessment, the sensitivity and specificity of the FCSI were 90 per cent and 90.5 per cent, respectively. Cronbach's alpha for internal reliability of the FCSI score was 0.727. An estimate of the surgically treated and control dogs' FCSI scores were 105 (95 per cent CI 93 to 116) and 20 (95 per cent CI 4 to 37), respectively. The difference between the groups was significant (P
  • Niemela, Tytti Maaria; Tulamo, Riitta-Mari; Uriel Carmona, Jorge; Lopez, Catalina (2019)
    Background: Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory mediators, such as prostaglandin E-2, have been documented but especially the effects on synovial fluid anti-inflammatory mediators are less studied. In animal models hyaluronan has been demonstrated to reduce pain via protecting nociceptive nerve endings and by blocking pain receptor channels. However, the results obtained for pain-relief of human osteoarthritis are contradictory. The aim of the study was to measure the synovial fluid IL-1ra, PDGF-BB, TGF-beta(1) and TNF-alpha concentrations before and after surgically induced cartilage defect, and following intra-articular hyaluronan injection in horses. Eight Standardbred horses underwent bilateral arthroscopic surgeries of their intercarpal joints under general anaesthesia, and cartilage defect was created on the dorsal edge of the third carpal bone of one randomly selected intercarpal joint of each horse. Five days post-surgery, one randomly selected intercarpal joint was injected intra-articular with 3 mL HA (20 mg/mL). Results: Operation type had no significant effect on the synovial fluid IL-1ra, PDGF-BB, TGF-beta(1) and TNF-alpha concentrations but compared with baseline, synovial fluid IL-1ra and TNF-alpha concentrations increased. Intra-articular hyaluronan had no significant effect on the biomarker concentrations but a trend of mild improvement in the clinical signs of intra-articular inflammation was seen. Conclusions: Creation of the cartilage defect and sham-operation lead to an increase of synovial fluid IL-1ra and TNF-alpha concentrations but changes in concentrations of anabolic growth factors TGF-beta(1) and PDGF-BB could not be documented 5 days after the arthroscopy. Intra-articular hyaluronan was well tolerated. Further research is needed to document possible treatment effects of intra-articular hyaluronan on the synovial fluid biomarkers of inflammation and cartilage metabolism.
  • Manderbacka, Kristiina; Satokangas, Markku; Arffman, Martti; Reissell, Eeva; Keskimäki, Ilmo; Leyland, Alastair H. (2022)
    Background A persistent research finding in industrialised countries has been regional variation in medical practices including elective primary hip and knee arthroplasty. The aim of the study was to examine regional variations in elective total hip and knee arthroplasties over time, and the proportions of these variations which can be explained by individual level or area-level differences in need. Methods We obtained secondary data from the Care Register for Health Care to study elective primary hip and knee arthroplasties in total Finnish population aged 25 + years between 2010 and 2017. Two-level Poisson regression models - individuals and hospital regions - were used to study regional differences in the incidence of elective hip and knee arthroplasties in two time periods: 2010 - 2013 and 2014 - 2017. The impact of several individual level explanatory factors (age, socioeconomic position, comorbidities) and area-level factors (need and supply of operations) was measured with the proportional change in variance. Predictions of incidence were measured with incidence rate ratios. The relative differences in risk of the procedures in regions were described with median rate ratios. Results We found small and over time relatively stable regional variation in hip arthroplasties in Finland, while the variation was larger in knee arthroplasties and decreased during the study period. In 2010 - 2013 individual socioeconomic variables explained 10% of variation in hip and 4% in knee arthroplasties, an effect that did not emerge in 2014 - 2017. The area-level musculoskeletal disorder index reflecting the need for care explained a further 44% of the variation in hip arthroplasties in 2010 - 2013, but only 5% in 2014 - 2017 and respectively 22% and 25% in knee arthroplasties. However, our final models explained the regional differences only partially. Conclusions Our results suggest that eligibility criteria in total hip and knee arthroplasty are increasingly consistent between Finnish hospital districts. Factors related to individual level and regional level need both had an important role in explaining regional variations. Further study is needed on the effect of health policy on equity in access to care in these operations.
  • Barreto, Goncalo; Soliymani, Rabah; Baumann, Marc; Waris, Eero; Eklund, Kari K; Zenobi-Wong, Marcy; Lalowski, Maciej (2019)
  • Junno, Juho-Antti; Keisu, Asla; Niinimäki, Maarit; Niinimäki, Jaakko; Lehenkari, Petri; Oura, Petteri (2022)
    Gestation increases the biomechanical loading of lower extremities. Gestational loading may influence anthropometrics of articular surfaces in similar means as bone diaphyseal properties. This study aimed to investigate whether gravidity (i.e. number of pregnancies) and parity (i.e. number of deliveries) is associated with knee breadth among middle-aged women. The study sample comprised 815 women from the Northern Finland Birth Cohort 1966. The median parity count of our sample was 2 and the median gravidity count 3. At the age of 46, questionnaires were used to enquire gravidity and parity, and posteroanterior knee radiographs were used to obtain two knee breadth parameters (tibial plateau mediolateral breadth (TPML) and femoral condylar mediolateral breadth (FCML)) as representatives of articular size. The associations of gravidity and parity with knee breadth were analyzed using general linear models with adjustments for height, weight, leisure-time physical activity, smoking, and education years. Individuals with osteoarthritic changes were excluded from our sample. The mean TPML in our sample was 70.3 mm and the mean FCML 71.6 mm respectively. In the fully adjusted models, gravidity and parity showed positive associations with knee breadth. Each pregnancy was associated with 0.11–0.14% larger knee breath (p < 0.05), and each delivery accounted for an increase of 0.20% in knee breadth (p < 0.01). Between-group comparisons showed that multiparous women had 0.68–1.01% larger knee breath than nulli- and primiparous women (p < 0.05). Pregnancies and deliveries seem to increase the mediolateral breadth of the knee. This increase is potentially associated with increased biomechanical loadings during gestation.
  • Kestilä, I.; Thevenot, J.; Finnilä, M. A.; Karhula, S. S.; Hadjab, I.; Kauppinen, S.; Garon, M.; Quenneville, E.; Haapea, M.; Rieppo, L.; Pritzker, K. P.; Buschmann, M. D.; Nieminen, H. J.; Saarakkala, S. (2018)
    Objective: The aims of this study were: to 1) develop a novel sample processing protocol to visualize human articular cartilage (AC) chondrons using micro-computed tomography (mu CT), 2) develop and validate an algorithm to quantify the chondron morphology in 3D, and 3) compare the differences in chondron morphology between intact and osteoarthritic AC. Method: The developed protocol is based on the dehydration of samples with hexamethyldisilazane (HMDS), followed by imaging with a desktop mCT. Chondron density and depth, as well as volume and sphericity, were calculated in 3D with a custom-made and validated algorithm employing semiautomatic chondron selection and segmentation. The quantitative parameters were analyzed at three AC depth zones (zone 1: 0-10%; zone 2: 10-40%; zone 3: 40-100%) and grouped by the OARSI histological grades (OARSI grades 0-1.0, n = 6; OARSI grades 3.0-3.5, n = 6). Results: After semi-automatic chondron selection and segmentation, 1510 chondrons were approved for 3D morphometric analyses. The chondrons especially in the deeper tissue (zones 2 and 3) were significantly larger (P Conclusion: We have developed a novel sample processing protocol for chondron imaging in 3D, as well as a high-throughput algorithm to semi-automatically quantify chondron/ chondrocyte 3D morphology in AC. Our results also suggest that 3D chondron morphology is affected by the progression of osteoarthritis (OA). (c) 2018 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (
  • Puhakka, Jani; Afara, Isaac O.; Paatela, Teemu; Sormaala, Markus J.; Timonen, Matti A.; Viren, Tuomas; Jurvelin, Jukka S.; Toyras, Juha; Kiviranta, Ilkka (2016)
    Objective. Accurate arthroscopic evaluation of cartilage lesions could significantly improve the outcome of repair surgery. In this study, we investigated for the first time the potential of intra-articular ultrasound as an arthroscopic tool for grading cartilage defects in the human shoulder joint in vivo and compared the outcome to results from arthroscopic evaluation and magnetic resonance imaging findings. Design. A total of 26 sites from 9 patients undergoing routine shoulder arthroscopy were quantitatively evaluated with a clinical intravascular (40MHz) ultrasound imaging system, using the regular arthroscopy portals. Reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB), and ultrasound roughness index (URI) were calculated, and high-resolution ultrasound images were obtained per site. Each site was visually graded according to the International Cartilage Repair Society (ICRS) system. "Ultrasound scores" corresponding to the ICRS system were determined from the ultrasound images. Magnetic resonance imaging was conducted and cartilage integrity at each site was classified into 5 grades (0 = normal, 4 = severely abnormal) by a radiologist. Results. R and IRC were lower at sites with damaged cartilage surface (P = 0.033 and P = 0.043, respectively) and correlated with arthroscopic ICRS grades (r (s) = -0.444, P = 0.023 and r (s) = -0.426, P = 0.03, respectively). Arthroscopic ICRS grades and ultrasound scores were significantly correlated (rs = 0.472, P = 0.015), but no significant correlation was found between magnetic resonance imaging data and other parameters. Conclusion. The results suggest that ultrasound arthroscopy could facilitate quantitative clinical appraisal of articular cartilage integrity in the shoulder joint and provide information on cartilage lesion depth and severity for quantitative diagnostics in surgery.
  • Miettinen, S. S. A.; Mäkinen, T. J.; Mäkelä, K.; Huhtala, H.; Kettunen, J. S.; Remes, V. (2018)
    Background and Aims: Large-diameter head total hip arthroplasty and hip resurfacing arthroplasty were popular in Finland from 2000 to 2012 for the treatment of hip osteoarthritis. The aim of this retrospective study was to investigate the mid-term survival of large-diameter head total hip arthroplasty patients operated on in three university hospitals and to compare these results to the survival of hip resurfacing arthroplasty patients. Material and Methods: A total of 3860 hip arthroplasties (3029 large-diameter head total hip arthroplasties in 2734 patients and 831 hip resurfacing arthroplasties in 757 patients) were operated on between January 2004 and December 2009. The mean follow-up was 4.3years (range: 0.3-8.0years) in the total hip arthroplasty group and 5.1years (range: 1.7-7.9years) in the hip resurfacing arthroplasty group. Cox multiple regression model and Kaplan-Meier survival analysis were used to study the survival of the total hip arthroplasties and the hip resurfacing arthroplasties. Intraoperative complications and reasons for revisions were also evaluated. Results: In Cox regression analysis, the hazard ratio for revision of hip resurfacing arthroplasty was 1.5 compared with large-diameter head total hip arthroplasty (95% confidence interval: 1.0-2.2) (p=0.029). The cumulative Kaplan-Meier survival rate was 90.7% at 7.7years for the large-diameter head total hip arthroplasty (95% confidence interval: 86.8-94.6) and 92.2% at 7.6years for hip resurfacing arthroplasty (95% confidence interval: 89.9-94.6). There were a total of 166/3029 (5.5%) intraoperative complications in the large-diameter head total hip arthroplasty group and 20/831 (2.4%) in the hip resurfacing arthroplasty group (p=0.001). Revision for any reason was performed on 137/3029 (4.5%) of the arthroplasties in the large-diameter head total hip arthroplasty group and 52/831 (6.3%) in the hip resurfacing arthroplasty group (p=0.04). Conclusion: The mid-term survival of both of these devices was poor, and revisions due to adverse reactions to metal debris will most likely rise at longer follow-up. There were more intraoperative complications in the large-diameter head total hip arthroplasty group than in the hip resurfacing arthroplasty group.
  • Göhre, Felix; Ludtka, Christopher; Hamperl, Melanie; Friedmann, Andrea; Straube, Anja; Mendel, Thomas; Heilmann, Andreas; Meisel, Hans Jorg; Schwan, Stefan (2017)
    Segmental degeneration in the human lumbar spine affects both the intervertebral discs and facet joints. Facet joint degeneration not only affects the cartilage surface, but also alters the cellular properties of the cartilage tissue and the structure of the subchondral bone. The primary focus of this study is the investigation of these microstructural changes that are caused by facet joint degeneration. Microstructural analyses of degenerated facet joint samples, obtained from patients following operative lumbar interbody fusion, have not previously been extensively investigated. This study analyzes human facet joint samples from the inferior articular process using scanning electron microscopy, micro-computed tomography, and energy dispersive X-ray spectroscopy to evaluate parameters of interest in facet joint degeneration such as elemental composition, cartilage layer thickness and cell density, calcification zone thickness, subchondral bone portion, and trabecular bone porosity. These microstructural analyses demonstrate fragmentation, cracking, and destruction of the cartilage layer, a thickened calcification zone, localized calcification areas, and cell cluster formation as pathological manifestations of facet joint degeneration. The detailed description of these microstructural changes is critical for a comprehensive understanding of the pathology of facet joint degeneration, as well as the subsequent development and efficacy analysis of regenerative treatment strategies.
  • Mikkola, Lea; Holopainen, Saila; Lappalainen, Anu; Pessa-Morikawa, Tiina; Pulikotial Augustine, Thomas; Arumilli, Meharji; Hytönen, Marjo Kristiina; Hakosalo, Osmo Topi Valtteri; Lohi, Hannes; Iivanainen, Antti (2019)
    Canine hip dysplasia is a common, non-congenital, complex and hereditary disorder. It can inflict severe pain via secondary osteoarthritis and lead to euthanasia. An analogous disorder exists in humans. The genetic background of hip dysplasia in both species has remained ambiguous despite rigorous studies. We aimed to investigate the genetic causes of this disorder in one of the high-risk breeds, the German Shepherd. We performed genetic analyses with carefully phenotyped case-control cohorts comprising 525 German Shepherds. In our genome-wide association studies we identified four suggestive loci on chromosomes 1 and 9. Targeted resequencing of the two loci on chromosome 9 from 24 affected and 24 control German Shepherds revealed deletions of variable sizes in a putative enhancer element of the NOG gene. NOG encodes for noggin, a well-described bone morphogenetic protein inhibitor affecting multiple developmental processes, including joint development. The deletion was associated with the healthy controls and mildly dysplastic dogs suggesting a protective role against canine hip dysplasia. Two enhancer variants displayed a decreased activity in a dual luciferase reporter assay. Our study identifies novel loci and candidate genes for canine hip dysplasia, with potential regulatory variants in the NOG gene. Further research is warranted to elucidate how the identified variants affect the expression of noggin in canine hips, and what the potential effects of the other identified loci are.
  • Pozharitskaya, Olga N.; Shikov, Alexander N.; Faustova, Natalya M.; Obluchinskaya, Ekaterina D.; Kosman, Vera M.; Vuorela, Heikki; Makarov, Valery G. (2018)
    Fucus vesiculosus L., known as bladderwrack, belongs to the brown seaweeds, which are widely distributed throughout northern Russia, Atlantic shores of Europe, the Baltic Sea, Greenland, the Azores, the Canary Islands, and shores of the Pacific Ocean. Fucoidan is a major fucose-rich sulfated polysaccharide found in Fucus (F.) vesiculosus. The pharmacokinetic profiling of active compounds is essential for drug development and approval. The aim of the study was to evaluate the pharmacokinetics and tissue distribution of fucoidan in rats after a single-dose oral administration. Fucoidan was isolated from F. vesiculosus. The method of measuring anti-activated factor X (anti-Xa) activity by amidolytic assay was used to analyze the plasma and tissue concentrations of fucoidan. The tissue distribution of fucoidan after intragastric administration to the rats was characterized, and it exhibited considerable heterogeneity. Fucoidan preferentially accumulates in the kidneys (AUC(0-t) = 10.74 mu g.h/g; C-max = 1.23 mu g/g after 5 h), spleen (AUC(0-t) = 6.89 mu g.h/g; C-max = 0.78 mu g/g after 3 h), and liver (AUC(0-t) = 3.26 mu g.h/g; C-max = 0.53 mu g/g after 2 h) and shows a relatively long absorption time and extended circulation in the blood, with a mean residence time (MRT) = 6.79 h. The outcome of this study provides additional scientific data for traditional use of fucoidan-containing plants and offers tangible support for the continued development of new effective pharmaceuticals using fucoidan.