Osteoclasts are recruited to the subchondral bone in naturally occurring post-traumatic equine carpal osteoarthritis and may contribute to cartilage degradation.
Abstract: The role of osteoclasts in osteochondral degeneration in osteoarthritis (OA) has rarely been investigated in spontaneous disease or animal models of OA. Objective: The objectives of the current study were to investigate osteoclast density and location in post-traumatic OA (PTOA) and control specimens from racehorses. Methods: Cores were harvested from a site in the equine third carpal bone, that undergoes repetitive, high intensity loading. Histological and immunohistochemical (Cathepsin K and Receptor-activator of Nuclear Factor kappa-β ligand (RANKL)) stained sections were scored (global and subregional) and the osteoclast density calculated. The cartilage histological scores were compared with osteoclast density and RANKL scores. Results: There was a greater density of osteoclasts in PTOA samples and they were preferentially located in the subchondral bone plate. RANKL scores positively correlated to the scores of cartilage degeneration and the osteoclast density. The relationship between hyaline articular cartilage RANKL score and osteoclast density was stronger than that of the subchondral bone RANKL score suggesting that cartilage RANKL may have a role in recruiting osteoclasts. The RANKL score in the articular calcified cartilage correlated with the number of microcracks also suggesting that osteoclasts recruited by RANKL may contribute to calcified cartilage degeneration in PTOA. Conclusions: Our results support the hypothesis that osteoclasts are recruited during the progression of spontaneous equine carpal PTOA by cartilage RANKL, contributing to calcified cartilage microcracks and focal subchondral bone loss.
Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Publication Date: 2015-10-24 PubMed ID: 26505663DOI: 10.1016/j.joca.2015.10.008Google Scholar: Lookup
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Summary
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This research article investigates the role of specialized bone cells, called osteoclasts, in the degeneration of tissues in a type of arthritis in horses caused by excessive wear and tear (post-traumatic osteoarthritis or PTOA). The findings suggest that these cells migrate to a specific area of the bone under the joint cartilage, contributing to its degradation. The activation of these osteoclasts is potentially driven by a specific signaling molecule, RANKL, found in the cartilage.
Background and Objective
- The article explores the role of osteoclasts, a type of cell responsible for bone resorption and remodelling, in PTOA, a common condition in racehorses characterized by joint disease following trauma.
- Previous research on osteoclasts’ involvement in OA has been sparse, hence this study aims to identify how the density and location of osteoclasts affect the cartilage’s condition in PTOA.
Methods
- The researchers derived samples from the third carpal bone of racehorses, an area undergoing regular, high intensity strain. Samples were then divided into PTOA and control specimens.
- These samples were then stained with specific substances to identify osteoclasts and RANKL, a signalling molecule associated with osteoclast activation and differentiation. Histological scoring was used to evaluate the results.
Results
- Findings showed that there were more osteoclasts in PTOA samples compared to control specimens. These osteoclasts were concentrated primarily in the bone beneath the joint cartilage (subchondral bone).
- RANKL scores, indicating the presence of the signalling molecule, were linked with cartilage degradation and more dense osteoclast populations.
- The relationship between cartilage RANKL score and osteoclast density was more potent than the corresponding relationship in the subchondral bone, suggesting that cartilage RANKL might be responsible for attracting osteoclasts.
- The number of small fractures in the bone lining under the cartilage also correlated with the RANKL score, indicating that the recruited osteoclasts might contribute to the degradation of this calcified cartilage in PTOA.
Conclusions
- The study provides evidence supporting the theory that osteoclasts are attracted during the progression of PTOA in the bone under the cartilage (the subchondral bone). This migration, potentially instigated by RANKL present in the cartilage, may contribute to the formation of small fractures in the calcified cartilage and localized bone loss in PTOA.
Cite This Article
APA
Bertuglia A, Lacourt M, Girard C, Beauchamp G, Richard H, Laverty S.
(2015).
Osteoclasts are recruited to the subchondral bone in naturally occurring post-traumatic equine carpal osteoarthritis and may contribute to cartilage degradation.
Osteoarthritis Cartilage, 24(3), 555-566.
https://doi.org/10.1016/j.joca.2015.10.008 Publication
Researcher Affiliations
- Comparative Orthopaedic Research Laboratory, Département de sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Rue Sicotte, St-Hyacinthe, QC J2S 2M2, Canada. Electronic address: andrea.bertuglia@unito.it.
- Comparative Orthopaedic Research Laboratory, Département de sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Rue Sicotte, St-Hyacinthe, QC J2S 2M2, Canada.
- Département de Pathologie et Microbiologie Vétérinaires, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Rue Sicotte, St-Hyacinthe, QC J2S 2M2, Canada.
- Département de Pathologie et Microbiologie Vétérinaires, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Rue Sicotte, St-Hyacinthe, QC J2S 2M2, Canada.
- Comparative Orthopaedic Research Laboratory, Département de sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Rue Sicotte, St-Hyacinthe, QC J2S 2M2, Canada.
- Comparative Orthopaedic Research Laboratory, Département de sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Rue Sicotte, St-Hyacinthe, QC J2S 2M2, Canada. Electronic address: sheila.laverty@umontreal.ca.
MeSH Terms
- Animals
- Calcinosis / metabolism
- Calcinosis / pathology
- Carpal Bones / metabolism
- Carpal Bones / pathology
- Carpal Joints / injuries
- Carpal Joints / pathology
- Cartilage Diseases / etiology
- Cartilage Diseases / metabolism
- Cartilage Diseases / pathology
- Cartilage Diseases / veterinary
- Cartilage, Articular / metabolism
- Cartilage, Articular / pathology
- Cell Count
- Cell Movement / physiology
- Horse Diseases / pathology
- Horses
- Male
- Osteoarthritis / etiology
- Osteoarthritis / metabolism
- Osteoarthritis / pathology
- Osteoarthritis / veterinary
- Osteoclasts / pathology
- Osteoclasts / physiology
- RANK Ligand / metabolism
- RANK Ligand / physiology
Citations
This article has been cited 40 times.- Dilley JE, Bello MA, Roman N, McKinley T, Sankar U. Post-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation. Bone Rep 2023 Jun;18:101658.
- Zhang H, Wang L, Cui J, Wang S, Han Y, Shao H, Wang C, Hu Y, Li X, Zhou Q, Guo J, Zhuang X, Sheng S, Zhang T, Zhou D, Chen J, Wang F, Gao Q, Jing Y, Chen X, Su J. Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression. Sci Adv 2023 Apr 5;9(14):eabo7868.
- Shi X, Mai Y, Fang X, Wang Z, Xue S, Chen H, Dang Q, Wang X, Tang S, Ding C, Zhu Z. Bone marrow lesions in osteoarthritis: From basic science to clinical implications. Bone Rep 2023 Jun;18:101667.
- Wang W, Ye R, Xie W, Zhang Y, An S, Li Y, Zhou Y. Roles of the calcified cartilage layer and its tissue engineering reconstruction in osteoarthritis treatment. Front Bioeng Biotechnol 2022;10:911281.
- Clarke EJ, Lima C, Anderson JR, Castanheira C, Beckett A, James V, Hyett J, Goodacre R, Peffers MJ. Optical photothermal infrared spectroscopy can differentiate equine osteoarthritic plasma extracellular vesicles from healthy controls. Anal Methods 2022 Sep 29;14(37):3661-3670.
- Chen R, Li X, Sun Z, Yin J, Hu X, Deng J, Liu X. Intra-bone marrow injection of magnesium isoglyrrhizinate inhibits inflammation and delays osteoarthritis progression through the NF-κB pathway. J Orthop Surg Res 2022 Aug 31;17(1):400.
- Chu M, Gao T, Zhang X, Kang W, Feng Y, Cai Z, Wu P. Elucidation of Potential Targets of San-Miao-San in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking Analysis. Evid Based Complement Alternat Med 2022;2022:7663212.
- Larrouture QC, Cribbs AP, Rao SR, Philpott M, Snelling SJ, Knowles HJ. Loss of mutual protection between human osteoclasts and chondrocytes in damaged joints initiates osteoclast-mediated cartilage degradation by MMPs. Sci Rep 2021 Nov 22;11(1):22708.
- Zhang L, Kirkwood CL, Sohn J, Lau A, Bayers-Thering M, Bali SK, Rachala S, Marzo JM, Anders MJ, Beier F, Kirkwood KL. Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling. Arthritis Res Ther 2021 Nov 16;23(1):287.
- Siriarchavatana P, Kruger MC, Miller MR, Tian H, Wolber FM. Non-polar lipid from greenshell mussel (Perna canaliculus) inhibits osteoclast differentiation. Bone Rep 2021 Dec;15:101132.
- Belenska-Todorova L, Lambova SN, Stoyanova S, Georgieva E, Batsalova T, Moten D, Kolchakova D, Dzhambazov B. Disease-Modifying Potential of Metformin and Alendronate in an Experimental Mouse Model of Osteoarthritis. Biomedicines 2021 Aug 15;9(8).
- Wang T, Guo Y, Shi XW, Gao Y, Zhang JY, Wang CJ, Yang X, Shu Q, Chen XL, Fu XY, Xie WS, Zhang Y, Li B, Guo CQ. Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway. Evid Based Complement Alternat Med 2021;2021:8168657.
- Ching K, Houard X, Berenbaum F, Wen C. Hypertension meets osteoarthritis - revisiting the vascular aetiology hypothesis. Nat Rev Rheumatol 2021 Sep;17(9):533-549.
- Zhuang C, Wang Z, Chen W, Tian B, Li J, Lin H. Osteoporosis and Endplate Damage Correlation Using a Combined Approach of Hounsfield Unit Values and Total Endplate Scores: A Retrospective Cross-Sectional Study. Clin Interv Aging 2021;16:1275-1283.
- Sun K, Zhu J, Deng Y, Xu X, Kong F, Sun X, Huan L, Ren C, Sun J, Shi J. Gamabufotalin Inhibits Osteoclastgenesis and Counteracts Estrogen-Deficient Bone Loss in Mice by Suppressing RANKL-Induced NF-κB and ERK/MAPK Pathways. Front Pharmacol 2021;12:629968.
- Huang T, Zhao C, Zhao Y, Zhou Y, Wang L, Hang D. RO4929097 regulates RANKL-induced osteoclast formation and LPS-mediated bone resorption. Aging (Albany NY) 2021 May 2;13(9):12526-12536.
- Mitton-Fitzgerald E, Gohr CM, Williams CJ, Ortiz A, Mbalaviele G, Rosenthal AK. Effects of the TNFRSF11B Mutation Associated With Calcium Pyrophosphate Deposition Disease in Osteoclastogenesis in a Murine Model. Arthritis Rheumatol 2021 Aug;73(8):1543-1549.
- Duan L, Liang Y, Xu X, Wang J, Li X, Sun D, Deng Z, Li W, Wang D. Noncoding RNAs in subchondral bone osteoclast function and their therapeutic potential for osteoarthritis. Arthritis Res Ther 2020 Nov 25;22(1):279.
- Dai G, Xiao H, Liao J, Zhou N, Zhao C, Xu W, Xu W, Liang X, Huang W. Osteocyte TGFβ1‑Smad2/3 is positively associated with bone turnover parameters in subchondral bone of advanced osteoarthritis. Int J Mol Med 2020 Jul;46(1):167-178.
- Su W, Liu G, Liu X, Zhou Y, Sun Q, Zhen G, Wang X, Hu Y, Gao P, Demehri S, Cao X, Wan M. Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development. JCI Insight 2020 Apr 23;5(8).
- Gao X, Sun Y, Li X. Identification of key gene modules and transcription factors for human osteoarthritis by weighted gene co-expression network analysis. Exp Ther Med 2019 Oct;18(4):2479-2490.
- Kovács B, Vajda E, Nagy EE. Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis. Int J Mol Sci 2019 Sep 19;20(18).
- Togni L, de Abreu MC, Augustin AH, da Silva RBM, Campos MM. Characterization of a rat model with temporomandibular joint osteoarthritis following a surgical anterior disc displacement. Am J Transl Res 2018;10(11):3806-3817.
- Donahue SW. Krogh's principle for musculoskeletal physiology and pathology. J Musculoskelet Neuronal Interact 2018 Sep 1;18(3):284-291.
- Löfvall H, Newbould H, Karsdal MA, Dziegiel MH, Richter J, Henriksen K, Thudium CS. Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes. Arthritis Res Ther 2018 Apr 10;20(1):67.
- Gao Y, Ge W. The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects against osteoporosis. Cell Death Dis 2018 Jan 18;9(2):33.
- Liu C, Liu C, Ren X, Si L, Shen H, Wang Q, Yao W. Quantitative evaluation of subchondral bone microarchitecture in knee osteoarthritis using 3T MRI. BMC Musculoskelet Disord 2017 Nov 28;18(1):496.
- Moritake A, Kawao N, Okada K, Tatsumi K, Ishida M, Okumoto K, Matsuo O, Akagi M, Kaji H. Plasminogen activator inhibitor-1 deficiency enhances subchondral osteopenia after induction of osteoarthritis in mice. BMC Musculoskelet Disord 2017 Sep 11;18(1):392.
- Findlay DM, Kuliwaba JS. Bone-cartilage crosstalk: a conversation for understanding osteoarthritis. Bone Res 2016;4:16028.
- Tang C, Sittplangkoon C, Xiang C, Schnur L, Duan R, Lin X, Li D, Yao Z. Evaluating Osteoarthritis Severity in Mice Using μCT-Derived Geometric Indices. Biology (Basel) 2026 Jan 31;15(3).
- Wang YH, Su CH, Chen LC, Liu JF, Tsai CH, Fong YC, Ko CY, Chen HT, Lo LC, Tang CH. miR-548aj-3p and miR-3127-3p suppress RANKL-facilitated inflammatory cytokines and catabolic factor in osteoarthritis and rheumatoid arthritis. Int J Med Sci 2025;22(14):3650-3663.
- Chen S, Long Y, Guo Z, Di J, Xu J, Xiang C. Pathophysiological Insights Into the Role of Osteoclasts in Osteoarthritis: Mechanisms, Therapeutic Targets, and Future Directions. J Inflamm Res 2025;18:11191-11204.
- Di Cicco G, Marzano E, Mastrostefano A, Pitocco D, Castilho RS, Zambelli R, Mascio A, Greco T, Cinelli V, Comisi C, Maccauro G, Perisano C. The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies. Biomedicines 2024 Oct 10;12(10).
- Ehrnsperger M, Taheri S, Pann P, Schilling AF, Grässel S. Differential effects of alendronate on chondrocytes, cartilage matrix and subchondral bone structure in surgically induced osteoarthritis in mice. Sci Rep 2024 Oct 23;14(1):25026.
- Liang W, Feng R, Li X, Duan X, Feng S, Chen J, Li Y, Chen J, Liu Z, Wang X, Ruan G, Tang S, Ding C, Huang B, Zou Z, Chen T. A RANKL-UCHL1-sCD13 negative feedback loop limits osteoclastogenesis in subchondral bone to prevent osteoarthritis progression. Nat Commun 2024 Oct 10;15(1):8792.
- Zhu Y, Cao L, Yuan M, Chen X, Xie X, Li M, Yang C, Wang X, Ma Z. Microgel Encapsulated Mesoporous Silica Nanoparticles for Releasing Wnt16 to Synergistically Treat Temporomandibular Joint Osteoarthritis. Adv Sci (Weinh) 2024 Nov;11(41):e2404396.
- Li TQ, Liu Y, Feng C, Bai J, Wang ZR, Zhang XY, Wang XX. Saikosaponin A attenuates osteoclastogenesis and bone loss by inducing ferroptosis. Front Mol Biosci 2024;11:1390257.
- Lin ST, Foote AK, Bolas NM, Sargan DR, Murray RC. Histological and Histopathological Features of the Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove in Thoroughbred Horses with Racing History. Animals (Basel) 2024 Jun 30;14(13).
- Chen Y, Cheng RJ, Wu Y, Huang D, Li Y, Liu Y. Advances in Stem Cell-Based Therapies in the Treatment of Osteoarthritis. Int J Mol Sci 2023 Dec 28;25(1).
- Mullin BH, Zhu K, Brown SJ, Mullin S, Dudbridge F, Pavlos NJ, Richards JB, Grundberg E, Bell JT, Zeggini E, Walsh JP, Xu J, Wilson SG. Leveraging osteoclast genetic regulatory data to identify genes with a role in osteoarthritis. Genetics 2023 Oct 4;225(2).
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