University of Oulu

Finnilä, M.A.J., Das Gupta, S., Turunen, M.J., Hellberg, I., Turkiewicz, A., Lutz-Bueno, V., Jonsson, E., Holler, M., Ali, N., Hughes, V., Isaksson, H., Tjörnstrand, J., Önnerfjord, P., Guizar-Sicairos, M., Saarakkala, S. and Englund, M. (2022), Mineral Crystal Thickness in Calcified Cartilage and Subchondral Bone in Healthy and Osteoarthritic Human Knees. J Bone Miner Res, 37: 1700-1710.

Mineral crystal thickness in calcified cartilage and subchondral bone in healthy and osteoarthritic human knees

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Author: Finnilä, Mikko A.J.1,2; Das Gupta, Shuvashis1; Turunen, Mikael J.3;
Organizations: 1Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
2Medical Research Center, University of Oulu, Oulu, Finland
3Department of Applied Physics, Faculty of Science and Forestry, University of Eastern Finland, Kuopio, Finland
4Clinical Epidemiology Unit, Orthopaedics, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden
5Paul Scherrer Institut, Villigen PSI, Switzerland
6Department of Biomedical Engineering, Lund University, Lund, Sweden
7Department of Orthopaedics, Skåne University Hospital, Lund, Sweden
8Rheumatology and Molecular Skeletal Biology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden
9Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.5 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2023-06-19


Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Series: Journal of bone and mineral research
ISSN: 0884-0431
ISSN-E: 1523-4681
ISSN-L: 0884-0431
Volume: 37
Issue: 9
Pages: 1700 - 1710
DOI: 10.1002/jbmr.4642
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
Funding: Author MAJF received funding for this work from the Finnish Cultural Foundation (North Ostrobothnia Regional Fund No. 60172246). Author SDG was supported by funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 713645. Author IH was supported by funding from the Finnish Foundation for Technology Promotion. Author HI acknowledge funding from the Swedish Research Council (2019-00953) under the frame of ERA PerMed. Author SS acknowledges grants from the Academy of Finland (Grants No. 268378, and 303786) and grants from the European Research Council under the European Union's Seventh Framework Program (FP/2007–2013; ERC Grant Agreement No. 336267), during conduction of this study. Author ME acknowledges grant support from the Swedish Research Council, The Swedish Rheumatology Association, Österlund Foundation, and the Governmental funding of clinical research within the national health services (ALF); other authors have no disclosures in relation to this manuscript. We acknowledge the Paul Scherrer Institut, Villigen PSI, Switzerland for the provision of synchrotron radiation beamtime at the cSAXS beamline X12SA of the SLS. Moreover, we thank Ms. Tarja Huhta for preparing the histological sections.
EU Grant Number: (713645) BioMEP - Biomedical Engineering and Medical Physics
(336267) 3D-OA-HISTO - Development of 3D Histopathological Grading of Osteoarthritis
Academy of Finland Grant Number: 268378
Detailed Information: 268378 (Academy of Finland Funding decision)
303786 (Academy of Finland Funding decision)
Dataset Reference: Data used for this study can be made available by submitting on reasonable request to the corresponding author.
Copyright information: © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.