The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the mouse
Open accessAbstract
Aim To describe a histologic scoring system for murine osteoarthritis (OA) that can be applied universally to instability, enzymatic, transgenic and spontaneous OA models.Methods Scientists with expertise in assessing murine OA histopathology reviewed the merits and drawbacks of methods described in the literature. A semi-quantitative scoring system that could reasonably be employed in any basic cartilage histology laboratory was proposed. This scoring system was applied to a set of 10 images of the medial tibial plateau and femoral condyle to yield 20 scores. These images were scored twice by four experienced scorers (CL, SG, MC, TA), with a minimum time interval of 1 week between scores to obtain intra-observer variability. An additional three novice scorers (CR, CL and MM) with no previous experience evaluated the images to determine the ease of use and reproducibility across laboratories.Results The semi-quantitative scoring system was relatively easy to apply for both experienced and novice scorers and the results had low inter- and intra-scorer variability. The variation in scores across both the experienced and novice scorers was low for both tibia and femur, with the tibia always having greater consistency.Conclusions The semi-quantitative scoring system recommended here is simple to apply and required no specialized equipment. Scoring of the tibial plateaus was highly reproducible and more consistent than that of the femur due to the much thinner femoral cartilage. This scoring system may be a useful tool for both new and experienced scorers to sensitively evaluate models and OA mechanisms, and also provide a common paradigm for comparative evaluation across the many groups performing these analyses.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Histological assessment of the medial tibial plateau joint was performed through blinded graded observations by two observers following OARSI scoring.
“histological assessment of the medial tibial plateau joint through blinded graded observations by two observers who followed the Osteoarthritis Research Society International (OARSI) scoring system35”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [35]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis
Glasson, S. S., Askew, R., Sheppard, B. J., Carito, B. A., Blanchet, T., Ma, H., Flannery, C. R., Peluso, D., Kanki, K., Yang, Z., et al. (2005) · Nature · doi:10.1038/nature03369 · Cited by 1,258 · see citing works
Self-citationOsteoarthritis development in novel experimental mouse models induced by knee joint instability
Kamekura, S., Hoshi, K., Shimoaka, T., Chung, U., Chikuda, H., Yamada, T., Uchida, M., Ogata, N., Seichi, A., Nakamura, K., et al. (2005) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2005.03.004 · Cited by 583 · see citing works
Neuhold, L. A., Killar, L. M., Zhao, W., Sung, M.-L. A., Warner, L. F., Kulik, J., Turner, J. R., Wu, W. K. K., Billinghurst, C., Meijers, T. H. M., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10564 · Cited by 541 · see citing works
Characterization of and osteoarthritis susceptibility in ADAMTS‐4–knockout mice
Glasson, S. S., Askew, R., Sheppard, B., et al. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20558 · Cited by 283 · see citing works
Self-citationWolfe, F., & Sharp, J. T. (1998) · Arthritis & Rheumatism · doi:10.1002/1529-0131(199809)41:9 · Cited by 274 · see citing works
Rudolphi, K. A., Gerwin, N., Verzijl, N., van der Kraan, P., & van den Berg, W. (2003) · Osteoarthritis and Cartilage · doi:10.1016/s1063-4584(03)00153-5 · Cited by 213 · see citing works
Scale effects in animal joints. I. articular cartilage thickness and compressive stress
Simon, W. H. (1970) · Arthritis & Rheumatism · doi:10.1002/art.1780130305 · Cited by 177 · see citing works
Botter, S. M., Glasson, S. S., Hopkins, B., et al. (2008) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2008.09.018 · Cited by 134 · see citing works
Self-citationChondrocyte cytokine and growth factor expression in murine osteoarthritis
Chambers, M., Bayliss, M. T., & Mason, R. M. (1997) · Osteoarthritis and Cartilage · doi:10.1016/s1063-4584(97)80034-9 · Cited by 130 · see citing works
Self-citationDegenerative joint disease in the mouse knee; histological observations
Walton, M. (1977) · The Journal of Pathology · doi:10.1002/path.1711230207 · Cited by 129 · see citing works
Experimental models of osteoarthritis.
Schwartz, E. R., & Greenwald, R. A. (1980) · PubMed · Cited by 125 · see citing works
Biochemical and Metabolic Aspects of Osteoarthritis
Mankin, H. J. (1971) · Orthopedic Clinics of North America · doi:10.1016/s0030-5898(20)31137-8 · Cited by 105 · see citing works
The role of structural genes in the pathogenesis of osteoarthritic disorders.
Reginato, A. M., & Olsen, B. R. (2002) · Arthritis Research · doi:10.1186/ar595 · Cited by 102 · see citing works
Age changes of bones and joints in various strains of mice
Silberberg, M., & Silberberg, R. (1941) · American Journal of Anatomy · doi:10.1002/aja.1000680104 · Cited by 79 · see citing works
Lapveteläinen, T., Nevalainen, T. O., Parkkinen, J. J., et al. (1995) · The Anatomical Record · doi:10.1002/ar.1092420204 · Cited by 69 · see citing works
Wilhelmi, G., & Faust, R. (2008) · Pharmacology · doi:10.1159/000136607 · Cited by 59 · see citing works
Sokoloff, L. (1956) · PubMed · Cited by 57 · see citing works
Premature osteoarthritis in the Disproportionate micromelia (Dmm) mouse
Bomsta, B. D., Bridgewater, L. C., & Seegmiller, R. E. (2006) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2005.11.011 · Cited by 50 · see citing works
Sexual dimorphism in the osteoarthritis of STR/ort mice may be linked to articular cytokines
Mahr, S., Menard, J., Krenn, V., et al. (2003) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2002.005041 · Cited by 36 · see citing works
JAY, G. E., & Sokoloff, L. (1956) · PubMed · Cited by 36 · see citing works
Osteoarthrosis and Osteoporosis in Senile Mice
Silberberg, M., & Silberberg, R. (2009) · Gerontologia · doi:10.1159/000211110 · Cited by 34 · see citing works
Epiphyseal Growth and Osteoarthrosis in Blotchy Mice
Silberberg, R. (2008) · Experimental Cell Biology · doi:10.1159/000162853 · Cited by 14 · see citing works
Blotchy mice: a model of osteoarthritis associated with a metabolic defect
Glasson, S. S., Trubetskoy, O. V., Harlan, P. M., et al. (1996) · Osteoarthritis and Cartilage · doi:10.1016/s1063-4584(96)80017-3 · Cited by 12 · see citing works
Self-citationAnalysis of Arthritic Lesions in the Del1 Mouse
Säämänen, A., Hyttinen, M. M., & VUORIO, E. I. (2007) · Methods in molecular medicine · doi:10.1007/978-1-59745-402-5_21 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Visco DM, Orevillo CJ, Kammerman J, Kincaid SA, Widmer WR, Christen AJ, et al. Is the murine partial medial meniscectomy model a useful model? Trans Orthop Res Soc 1998;23:876.
- Brewster M, Lewis EJ, Wilson KL, Greenham AK, Bottomley KM. Ro 32-3555, an orally active collagenase selective inhibitor, prevents structural damage in the STR/ORT mouse model of osteoarthritis. Arthritis Rheum 1998;41: 1639e44.
Cited by
Sorted by citations
Jeon, O. H., Kim, C., Laberge, R.-M., Demaria, M., Rathod, S., Vasserot, A. P., Chung, J. W., Kim, D. H., Poon, Y., David, N., et al. (2017) · Nature Medicine · doi:10.1038/nm.4324 · Cited by 1,515 · see citing works
Novais, E. J., Tran, V. A., Johnston, S. N., Darris, K. R., Roupas, A. J., Sessions, G. A., Shapiro, I. M., Diekman, B. O., & Risbud, M. V. (2021) · Nature Communications · doi:10.1038/s41467-021-25453-2 · Cited by 440 · see citing works
IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis
Faust, H. J., Zhang, H., Han, J., Wolf, M. T., Jeon, O. H., Sadtler, K., Peña, A. N., Chung, L., Maestas, D. R., Tam, A. J., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134091 · Cited by 260 · see citing works
Vasheghani, F., Zhang, Y., Li, Y.-H., Blati, M., Fahmi, H., Lussier, B., Roughley, P., Lagares, D., Endisha, H., Saffar, B., et al. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-205743 · Cited by 221 · see citing works
The relationship of autophagy defects to cartilage damage during joint aging in a mouse model
Caramés, B., Olmer, M., Kiosses, W. B., & Lotz, M. K. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39073 · Cited by 204 · see citing works
Proteoglycan 4 Expression Protects Against the Development of Osteoarthritis
Ruan, M. Z. C., Erez, A., Guse, K., Dawson, B., Bertin, T., Chen, Y., Jiang, M.-M., Yustein, J., Gannon, F., & Lee, B. H. L. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005409 · Cited by 196 · see citing works
Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy
Nogueira-Recalde, U., Lorenzo-Gómez, I., Blanco, F. J., Loza, M. I., Grassi, D., Shirinsky, V., Shirinsky, I., Lotz, M., Robbins, P. D., Domínguez, E., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.06.049 · Cited by 155 · see citing works
Osteoarthritis treatment via the GLP-1–mediated gut-joint axis targets intestinal FXR signaling
Yang, Y., Hao, C., Jiao, T., Yang, Z., Li, H., Zhang, Y., Zhang, W., Doherty, M., Sun, C., Yang, T., et al. (2025) · Science · doi:10.1126/science.adt0548 · Cited by 160 · see citing works
Zhao, S., Xiu, G., Wang, J., Wen, Y., Lu, J., Wu, B., Wang, G., Yang, D., Ling, B., Du, D., et al. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-02086-9 · Cited by 109 · see citing works
Vasheghani, F., Monemdjou, R., Fahmi, H., Zhang, Y., Perez, G., Blati, M., St-Arnaud, R., Pelletier, J.-P., Beier, F., Martel-Pelletier, J., et al. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.12.012 · Cited by 80 · see citing works
He, Z., Li, H., Han, X., Zhou, F., Du, J., Yang, Y., Xu, Q., Zhang, S., Zhang, S., Zhao, N., et al. (2020) · Bone · doi:10.1016/j.bone.2020.115573 · Cited by 76 · see citing works
La Porta, C., Bura, S. A., Aracil-Fernández, A., Manzanares, J., & Maldonado, R. (2013) · Pain · doi:10.1016/j.pain.2012.10.009 · Cited by 75 · see citing works
CCL3/CCR1 mediates CD14+CD16− circulating monocyte recruitment in knee osteoarthritis progression
Zhao, X., Gu, M., Xu, X., Wen, X., Yang, G., Li, L., Sheng, P., & Meng, F. (2020) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2020.01.009 · Cited by 66 · see citing works
The type 2 cannabinoid receptor regulates susceptibility to osteoarthritis in mice
Sophocleous, A., Börjesson, A. E., Salter, D. M., & Ralston, S. H. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.04.020 · Cited by 54 · see citing works
Sondergaard, B. C., Catala-Lehnen, P., Huebner, A. K., Bay-Jensen, A.-C., Schinke, T., Henriksen, K., Schilling, S., Haberland, M., Nielsen, R. H., Amling, M., et al. (2012) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2011.11.004 · Cited by 38 · see citing works
Albumin-binding RNAi Conjugate for Carrier Free Treatment of Arthritis
Colazo, J. M., Hoogenboezem, E. N., Keech, M. C., Francini, N., Shah, V., Yu, F., Lo, J. H., Sorets, A. G., McCune, J. T., Cho, H., et al. (2023) · doi:10.1101/2023.05.31.542971 · Cited by 11 · see citing works
Tokumoto, M., Nakasa, T., Shirakawa, Y., Nekomoto, A., Ikuta, Y., Ishikawa, M., Miyaki, S., & Adachi, N. (2023) · Connective Tissue Research · doi:10.1080/03008207.2022.2099847 · Cited by 4 · see citing works
- Authors
- Glasson, S. S., Chambers, M. G., Van Den Berg, W. B., & Little, C. B.
- Affiliations
- Pfizer (United States) (US)
- Eli Lilly (United States) (US)
- The University of Sydney (AU)
- Corresponding author
- Glasson, S.S.
- Chambers, M.G.
- Little, C.B.
- Venue
- Osteoarthritis and Cartilage
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 18
- Pages
- S17-S23
- ISSN
- 1063-4584 (ISSN-L)
- OpenAlex
- W4232024554
- Cited by
- 1,708
- References
- 24
- Citations by year
- 2026: 159 · 2025: 196 · 2024: 185 · 2023: 193 · 2022: 189 · 2021: 139 · 2020: 145 · 2019: 100 · 2018: 88 · 2017: 78 · 2016: 61 · 2015: 60 · 2014: 39 · 2013: 32 · 2012: 26
- FWCI
- 16.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Osteoarthritis and Cartilage (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- Servier
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Surgery › Hip disorders and treatments
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Keywords
- osteoarthritis, cartilage histopathology, interobserver variability, intraobserver variability, medial tibial plateau, femoral condyle, cartilage degeneration
- MeSH terms
- Animals, Arthritis, Experimental, Cartilage, Articular, Disease Models, Animal, Joints, Osteoarthritis, Proteoglycans, Severity of Illness Index, Synovial Membrane, Reproducibility of Results, Observer Variation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
