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| 2. |
- Ley, Charles, et al.
(författare)
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Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities.
- 2014
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Ingår i: eCells and Materials Journal. - 1473-2262. ; 27, s. 213-236
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Tidskriftsartikel (refereegranskat)abstract
- Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.
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| 3. |
- Skiöldebrand, Eva, et al.
(författare)
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Cartilage oligomeric matrix protein neoepitope in the synovial fluid of horses with acute lameness: A new biomarker for the early stages of osteoarthritis
- 2017
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Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 49:5, s. 662-667
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundClinical tools to diagnose the early changes of osteoarthritis (OA) that occur in the articular cartilage are lacking. ObjectivesWe sought to identify and quantify a novel cartilage oligomeric matrix protein (COMP) neoepitope in the synovial fluid from the joints of healthy horses and those with different stages of OA. Study designIn vitro quantitative proteomics and assay development with application in synovial fluids samples obtained from biobanks of well-characterised horses. MethodsArticular cartilage explants were incubated with or without interleukin-1 for 25 days. Media were analysed via quantitative proteomics. Synovial fluid was obtained from either normal joints (n = 15) or joints causing lameness (n = 17) or with structural OA lesions (n = 7) and analysed for concentrations of the COMP neoepitope using a custom-developed inhibition enzyme-linked immunosorbent assay (ELISA). Explants were immunostained with polyclonal antibodies against COMP and the COMP neoepitopes. ResultsSemitryptic COMP peptides were identified and quantified in cell culture media from cartilage explants. A rabbit polyclonal antibody was raised against the neoepitope of the N-terminal portion of one COMP fragment (sequence SGPTHEGVC). An inhibition ELISA was developed to quantify the COMP neoepitope in synovial fluid. The mean concentration of the COMP neoepitope significantly increased in the synovial fluid from the joints responsible for acute lameness compared with normal joints and the joints of chronically lame horses and in joints with chronic structural OA. Immunolabelling for the COMP neoepitope revealed a pericellular staining in the interleukin-1-stimulated explants. Main limitationsThe ELISA is based on polyclonal antisera rather than a monoclonal antibody. ConclusionsThe increase in the COMP neoepitope in the synovial fluid from horses with acute lameness suggests that this neoepitope has the potential to be a unique candidate biomarker for the early molecular changes in articular cartilage associated with OA.
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| 4. |
- Hedenqvist, Patricia, et al.
(författare)
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Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting
- 2016
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Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 107, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10 x 10 mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n = 9) or buprenorphine plus saline (n = 9) postoperatively. Buprenorphine was administered subcutaneously every 6 h for 3 days in a tapered dose (0.05-0.01 mg/kg) and carprofen (5 mg/kg) or saline administered subcutaneously 1 h before, and daily for 4 days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13 h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 43 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5 mg/kg carprofen once daily for 5 days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation.
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| 5. |
- Ekman, Stina
(författare)
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Local Morphological Response of the Distal Femoral Articular–Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children
- 2013
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Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 4, s. 239-248
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Describe the local morphological response of the articular-epiphyseal cartilage complex to surgical stab incision in the distal femur of foals, with emphasis on the relationship between growth cartilage injury, enchondral ossification, and repair. Design: Nine foals were induced into general anesthesia at the age of 13 to 15 days. Four full-thickness stab incision defects were created in the cartilage on the lateral aspect of the lateral trochlear ridge of the left distal femur. Follow-up examination was carried out from 1 to 49 days postoperatively, including examination of intact bones, sawed slabs, and histological sections. Results: Incision defects filled with cells displaying fibroblast-, chondrocyte-, and osteoblast-like characteristics, potentially validating the rationale behind the drilling of stable juvenile osteochondritis dissecans lesions in children. Incisions induced necrosis within the cartilage on the margins at all depths of the defects. Sharp dissection may therefore be contraindicated in cartilage repair in young individuals. Incisions caused a focal delay in enchondral ossification in 2 foals, apparently related to the orientation of the incision defect relative to the direction of ossification. Defects became progressively surrounded by subchondral bone, in which granulation tissue containing clasts and foci of osteoblast-like cells was observed. Continued enchondral ossification was therefore likely to result in healing of uncomplicated defects to morphologically normal bone. Conclusions: Epiphyseal growth cartilage injury had the potential to exert a negative effect on enchondral ossification. Enchondral ossification exerted a beneficial effect on repair. This relationship warrants consideration in future studies of cartilage injury and repair within the articular-epiphyseal cartilage complex of all species.
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| 6. |
- Ley, Charles, et al.
(författare)
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Evaluation of osteochondral sample collection guided by computed tomography and magnetic resonance imaging for early detection of osteoarthritis in centrodistal joints of young icelandic horses
- 2013
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Ingår i: Veterinary Radiology and Ultrasound. - 1058-8183 .- 1740-8261. ; 55, s. 1-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Histologic examination with light microscopy is considered the reference standard to detect osteoarthritis (OA) in its earliest stages1, 2. In early OA, articular cartilage changes develop in focal and specific regions of the affected joint3 but the locations of these regions in specific joints and species are uncertain and are likely to vary among individuals. When osteochondral samples are collected from predetermined anatomic sites for histologic examination of joints early in the disease process, then it is possible that OA will fail to be detected because the associated lesions may not be included in the collection site. This study evaluates a method for computed tomography (CT) and magnetic resonance imaging (MRI) guided osteochondral sample collection for the detection of early stage OA lesions in joints from young Icelandic horses. Materials and Methods: CT and MRI were semiquanitatively graded to evaluate the extent of suspected OA changes in right centrodistal joints from the cadavers of 24 Icelandic horses aged 29 to 31 months. The anatomic regions with the highest grade of change were identified, and osteochondral samples were obtained from these regions. Samples were also obtained from the same centrodistal joints at predetermined sites. Histologic examination of all samples was performed, with samples classified as negative or positive for OA, and results were compared between sample collection method. Results: Histologic examination revealed OA lesions in 29% (7/24) of centrodistal joints with predetermined method and in 62% (15/24) with the image-guided method. Significant associations were detected between histologic OA and the summed image-guided sample collection site image grades, central osteophytes, articular cartilage thickness abnormalities, grade-2 articular mineralisation front defects, and grade-2 marginal osteophytes. Discussion/Conclusion:An image-guided sample collection method is recommended when histologic examination will be used as the reference standard for the detection of early-stage OA in centrodistal joints of horses. CT and MRI aided the detection of focal changes suggestive of early stage OA in the centrodistal joints of equine cadavers and may be useful for detection of similar disease in live horses. The first morphological changes of centrodistal joint OA are suspected to be in the articular cartilage and the articular mineralisation front regions.
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| 7. |
- Engelsen Etterlin, Pernille, et al.
(författare)
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Osteochondrosis, Synovial Fossae, and Articular Indentations in the Talus and Distal Tibia of Growing Domestic Pigs and Wild Boars
- 2017
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Ingår i: Veterinary pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 54:3, s. 445-456
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Tidskriftsartikel (refereegranskat)abstract
- Articular osteochondrosis (OC) often develops in typical locations within joints, and the characterization of OC distribution in the pig tarsus is incomplete. Prevalence of OC is high in domestic pigs but is presumed to be low in wild boars. Postmortem and computed tomography (CT) examinations of the talus and distal tibia from 40 domestic pigs and 39 wild boars were evaluated for the locations and frequencies of OC, synovial fossae, and other articular indentations, and frequency distribution maps were made. All domestic pigs but only 5 wild boars (13%) had OC on the talus. In domestic pigs, OC consistently affected the axial aspect of the medial trochlea tali in 11 (28%) joints and the distomedial talus in 26 (65%) joints. In wild boars, all OC lesions consistently affected the distomedial talus. On the articular surface of the distal tibia, all domestic pigs and 34 wild boars (87%) had synovial fossae and 7 domestic pigs (18%) had superficial cartilage fibrillation opposite an OC lesion (kissing lesion). Other articular indentations occurred in the intertrochlear groove of the talus in all domestic pigs and 13 wild boars (33%) and were less common on the trochlea tali. The prevalence of tarsal OC in wild boars is low. In domestic pigs and wild boars, OC is typically localized to the distomedial talus and in domestic pigs also to the medial trochlea tali. Further investigations into the reasons for the low OC prevalence in wild boars may help in developing strategies to reduce OC incidence in domestic pigs.
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| 8. |
- Ley, Cecilia, et al.
(författare)
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Effects of high mobility group box protein-1, interleukin-1 beta, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures
- 2011
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Ingår i: Connective Tissue Research. - : Informa UK Limited. - 0300-8207 .- 1607-8438. ; 52, s. 290-300
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Tidskriftsartikel (refereegranskat)abstract
- The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1 beta, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1 beta treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1 beta-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1 beta, whereas slight anabolic effects were induced by IL-6 and HMGB-1.
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| 9. |
- Ley, Cecilia, et al.
(författare)
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Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures.
- 2011
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Ingår i: Connective tissue research. - : Informa UK Limited. - 1607-8438 .- 0300-8207. ; 52:4, s. 290-300
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Tidskriftsartikel (refereegranskat)abstract
- The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1β, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1β treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1β-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1β, whereas slight anabolic effects were induced by IL-6 and HMGB-1.
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| 10. |
- Löfgren, Maria, et al.
(författare)
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Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants
- 2023
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Ingår i: Equine Veterinary Journal. - : Wiley. - 0425-1644 .- 2042-3306. ; 55:2, s. 325-335
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated. Objectives: To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)-1 beta and cartilage explants with mild osteoarthritis. Study design: In vitro experimental study. Methods: The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h] and serum incubated 24 h in ACS containers [PCS]) pooled from lame horses were tested in two in vitro models. IL-1 beta and IL-1 receptor antagonist (IL-1Ra) concentrations were measured in all sera. In model 1, chondrocyte pellet cultures were stimulated with IL-1 beta prior to treatment with the serum preparations for 2 and 48 h. Microarray, polymerase chain reaction, and matrix metallopeptidase-13 analyses were performed. In model 2, cartilage explants from horses with structural osteoarthritis were treated with PS or PCS on days 0, 6 and 12, or left untreated, and evaluated at day 24 using the OARSI grading scale for histological evaluation of articular cartilage. Results: The IL-1Ra concentration in PS24h and PCS was significantly higher than in PS. In model 1, inflammation- and cartilage matrix degradation-related genes were upregulated after 48 h in all treatment groups versus untreated controls. Cartilage matrix molecules, aggrecan and collagens, were downregulated in PS24h- and PCS-treated pellets versus untreated controls. Growth factor signalling genes were upregulated-FGF7 in all treatment groups, BMP2 in PS24h-, and INHBA in PCS-treated-compared with untreated controls. In model 2, the OARSI score at day 24 was not significantly different between treatment groups. Main limitations: Results from in vitro models cannot be directly translated to in vivo situations. Conclusions: In vitro treatment with conditioned serum did not alleviate IL-1 beta-induced responses in chondrocyte pellets or lead to morphological improvement in osteoarthritic cartilage explants.
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