Glycosaminoglycan measured from synovial fluid serves as a useful indicator for progression of Osteoarthritis and complements Kellgren–Lawrence Score

Kulkarni, Priya; Deshpande, Shantanu; Koppikar, Soumya J.; Patil, Sanjay; Ingale, Dhanashri R; Harsulkar, Abhay

doi:10.1016/j.bbacli.2016.05.002

Cited by 26 publications

(27 citation statements)

References 12 publications

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“…We also evaluated concentrations of glycosaminoglycans (GAG) in synovial fluid by a spectrophotometric dye binding assay using 1,2, dimethylmethylene blue (DMMB; Santa Cruz Biotechnology) 46 . A positive correlation between GAG concentration in synovial fluid and KL grade was demonstrated in a previous report 28 .…”

Section: Methodssupporting

confidence: 63%

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Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis

Okura

Ohkawara

Takegami

et al. 2019

Sci Rep

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Aberrant activation of the Wnt/β-catenin signaling pathway promotes the progression of osteoarthritis (OA). We previously reported that R-spondin 2 (Rspo2), an activator of the Wnt/β-catenin signaling, facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification. However, the role of Rspo2 in OA remains elusive. Here, we showed that the amounts of Rspo2 protein in synovial fluid were increased in OA patients. We searched for a preapproved drug that suppresses Rspo2-induced Wnt/β-catenin signaling in chondrogenic cells and reduces joint pathology in a rat model of OA. In Rspo2-treated ATDC5 cells, mianserin, a tetracyclic antidepressant, inhibited Wnt/β-catenin signaling, increased proteoglycan production, and upregulated chondrogenic marker genes. Mianserin suppressed Rspo2-induced accumulation of β-catenin and phosphorylation of Lrp6. We identified that mianserin blocked binding of Rspo2 to its receptor Lgr5. We also observed that intraarticular administration of mianserin suppressed β-catenin accumulation and prevented OA progression in a rat model of OA. We conclude that mianserin suppresses abnormally activated Wnt/β-catenin signaling in OA by inhibiting binding of Rspo2 to Lgr5.

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Section: Methodssupporting

confidence: 63%

“…We first confirmed that glycosaminoglycans (GAG), which are degradation products of GAG chains in cartilage proteoglycans 28 , were increased in synovial fluid with increasing OA severities that was evaluated by the Kellgren-Lawrence (KL) radiographic grading system 29 (Fig. 1A–C).…”

Section: Resultsmentioning

confidence: 65%

Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis

Okura

Ohkawara

Takegami

et al. 2019

Sci Rep

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“…This improvement was also suggested by the lower concentration of GAGs in the synovial fluid of the intervention group joints. Indeed, a higher concentration of GAGs in synovial fluid indicates a release of GAGs from diseased articular cartilage into the synovial fluid, as is seen in naturally occurring OA [19,20].…”

Section: Discussionmentioning

confidence: 99%

The use of equine chondrogenic‐induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double‐blinded, placebo‐controlled proof‐of‐concept study

Broeckx

Martens

Bertone

et al. 2019

Equine Veterinary Journal

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Summary Background There is a need to improve therapies for osteoarthritis in horses. Objectives To assess the efficacy of equine allogeneic chondrogenic‐induced mesenchymal stem cells combined with equine allogeneic plasma as a novel therapy for osteoarthritis in horses. Study design Randomised, double‐blinded, placebo‐controlled experiment. Methods In 12 healthy horses, osteoarthritis was induced in the metacarpophalangeal joint using an osteochondral fragment‐groove model. Five weeks after surgery, horses were randomly assigned to either an intra‐articular injection with chondrogenic‐induced mesenchymal stem cells + equine allogeneic plasma (= intervention) or with 0.9% saline solution (= control). From surgery until the study end, horses underwent a weekly joint and lameness assessment. Synovial fluid was collected for cytology and biomarker analysis before surgery and at Weeks 5, 5 + 1d, 7, 9 and 11. At Week 11, horses were subjected to euthanasia, and the metacarpophalangeal joints were evaluated macroscopically and histologically. Results No serious adverse events or suspected adverse drug reactions occurred during the study. A significant improvement in visual and objective lameness was seen with the intervention compared with the control. Synovial fluid displayed a significantly higher viscosity and a significantly lower glycosaminoglycan concentration in the intervention group. Other biomarkers or cytology parameters were not significantly different between the treatment groups. Significantly less wear lines and synovial hyperaemia were present in the intervention group. The amount of cartilage oligomeric matrix protein, collagen type II and glycosaminoglycans were significantly higher in the articular cartilage of the intervention group. Main limitations This study assessed the short‐term effect of the intervention on a limited number of horses, using an osteoarthritis model. This study also included multiple statistical tests, increasing the risk of type 1 error. Conclusions Equine allogeneic chondrogenic‐induced mesenchymal stem cells combined with equine allogeneic plasma may be a promising treatment for osteoarthritis in horses. The Summary is available in Spanish – see Supporting Information

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“…Though, since gagCEST is temperature and pH dependent this would not have been a good choice in these ex vivo studies because those parameters are hard to keep controlled over various samples. 97 . This could be an important factor in the lack of correlation in our DMMB analyses versus sodium concentration, since mostly end-stage OA cartilage has been included.…”

Section: Discussionmentioning

confidence: 99%

“…When scraping off cartilage samples one easily includes some bone or parts of the calcified layer, increasing the overall weight of the sample but decreasing the (relative) amount of GAGs -spoiling the results with a too low GAG measurement. Additionally, at least in synovial fluid, DMMB analyses in end-stage OA seem to have two distinct categories: one with very high GAG content (possible active cartilage degeneration process) and one with very low GAG content (completely worn-out cartilage) 97 . These two causes could be the underlying factors of the lack of correlation of DMMB assays in the lateral condyle in chapter 6 or the samples used in chapter 3.…”

Section: Validationmentioning

confidence: 99%

Cartilage Properties Quantified With 7T MRI

Brinkhof¹

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Chapter 1 Introduction Chapter 2 Uncompromised MRI of knee cartilage while incorporating sensitive sodium MRI Chapter 3 Can sodium MRI be used as a method for mapping of cartilage stiffness? Chapter 4 T2* mapping in an equine articular groove modelvisualizing changes in collagen orientation Chapter 5 Detection of early cartilage damage: feasibility and potential of gagCEST imaging at 7T Chapter 6 In Vivo Cartilage Quantification with gagCEST MRI: Correlation with Cartilage Properties Chapter 7 Summary and general discussion Appendices General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General introduction General...

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Glycosaminoglycan measured from synovial fluid serves as a useful indicator for progression of Osteoarthritis and complements Kellgren–Lawrence Score

Cited by 26 publications

References 12 publications

Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis

Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis

The use of equine chondrogenic‐induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double‐blinded, placebo‐controlled proof‐of‐concept study

Cartilage Properties Quantified With 7T MRI

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