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Calcipotriol, a vitamin D analogue, is an antiproliferative and anti-inflammatory drug currently used in psoriasis. Here, our aim was to analyse the safety of calcipotriol for cartilage and bone in alleviated-dose (0.1 mg instead of usual ≥1mg dose) zymosan-induced arthritis in rats. Theoretically, high doses of vitamin D or analogues could have detrimental effects on bone or cartilage. The rats were divided into four groups: vehicle (n = 9), dexamethasone 0.1 mg/kg (n = 9), calcipotriol 0.1 mg/kg (n = 8) and negative control (n = 10) with no injections. Arthritic rats were given phosphate-buffered saline (PBS) injections to left knees as a control. After euthanasia on day 8, all knees were imaged with micro-computed tomography for surface lesions and decalcified for histological analyses. Contrary to our expectations, no significant changes could be observed in the tomography data and histological scores among the three treatment groups or between the vehicle-treated and non-arthritic group. Calcipotriol did not cause adverse effects on cartilage or subchondral bone within a week, suggesting that it could be safely used in local treatment of arthritis. The alleviated model caused synovitis with local and systemic inflammatory response without cartilage erosions, which might be useful in studying self-limiting synovitis where cartilage or bone effects are not of primary interest., (© 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

This study investigates the influence of osteoarthritis (OA) disease severity on the bio-composition of the osteochondral junction at the human tibial plateau using Raman microspectroscopy. We specifically aim to analyze the spatial composition of mineralized osteochondral tissues, i.e., calcified cartilage (CC) and subchondral bone plate (SBP) from unfixed, hydrated specimens. We hypothesize that the mineralization of CC and SBP decreases in advanced OA. Twenty-eight cylindrical osteochondral samples (d = 4 mm) from tibial plateaus of seven cadaveric donors were harvested and sorted into three groups following histopathological grading: healthy (n = 5), early OA (n = 8), and advanced OA (n = 15). Raman spectra were subjected to multivariate cluster analyses to identify different tissues. Finally, the tissue-specific composition was analyzed, and the impact of OA was statistically evaluated with linear mixed models. Cluster analyses of Raman spectra successfully distinguished CC and SBP as well as a tidemark region and uncalcified cartilage. CC was found to be more mineralized and the mineral was more crystalline compared with SBP. Both tissues exhibited similar compositional changes as a function of histopathological OA severity. In early OA, the mineralization tends to increase, and the mineral contains fewer carbonate substitutions. Compared with early OA, mineral crystals are rich in carbonate while the overall mineralization decreases in advanced OA. This Raman spectroscopic study advances the methodology for investigating the complex osteochondral junction from native tissue. The developed methodology can be used to elucidate detailed tissue-specific changes in the chemical composition with advancing OA. STATEMENT OF SIGNIFICANCE: In this study, Raman microspectroscopy was utilized to investigate the influence of osteoarthritic degeneration on the tissue-specific biochemical composition of the human osteochondral junction. Multivariate cluster analyses allowed us to characterize subtle compositional changes in the calcified cartilage and subchondral bone plate as well as in the tidemark region. The compositional differences found between the calcified cartilage and subchondral bone plate in both organic and mineral phases will serve as critical benchmark parameters when designing biomaterials for osteochondral repair. We found tissue-specific changes in the mineralization and carbonate substitution as a function of histopathological OA severity. Our developed methodology can be used to investigate the metabolic changes in the osteochondral junction associated with osteoarthritis., Competing Interests: Declaration of Competing Interest SS reports grants from the European Research Council (Grant Agreement number 336267) and grants from the Academy of Finland (Grant numbers 268378 & 303786), during the conduct of the study. LR reports grant from the Academy of Finland (project number 310466) during the conduct of the study. Other authors have no disclosures in relation to this manuscript., (Copyright © 2020. Published by Elsevier Ltd.)

Contrast-enhanced micro-computed tomography (CEμCT) 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 CEμCT 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 CEμCT 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 CEμCT method for 3D characterization of articular cartilage., Competing Interests: The authors have declared that no competing interests exist.