Review

. 2016 Feb 2:11:19.

doi: 10.1186/s13018-016-0346-5.

Animal models of osteoarthritis: classification, update, and measurement of outcomes

Emmanuel L Kuyinu^{1

2

3}, Ganesh Narayanan^{4

5

6}, Lakshmi S Nair^{7

8

9

10

11

12}, Cato T Laurencin^{13

14

15

16

17

18

19

20}

Affiliations

¹ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. kuyinu@uchc.edu.
² Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. kuyinu@uchc.edu.
³ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. kuyinu@uchc.edu.
⁴ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. gnarayanan@uchc.edu.
⁵ Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. gnarayanan@uchc.edu.
⁶ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. gnarayanan@uchc.edu.
⁷ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. Nair@uchc.edu.
⁸ Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. Nair@uchc.edu.
⁹ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. Nair@uchc.edu.
¹⁰ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA. Nair@uchc.edu.
¹¹ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, USA. Nair@uchc.edu.
¹² Institute of Materials Science, University of Connecticut, Storrs, CT, USA. Nair@uchc.edu.
¹³ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
¹⁴ Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
¹⁵ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
¹⁶ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.
¹⁷ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.
¹⁸ Institute of Materials Science, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.
¹⁹ Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
²⁰ Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.

PMID: 26837951
PMCID: PMC4738796
DOI: 10.1186/s13018-016-0346-5

Review

Animal models of osteoarthritis: classification, update, and measurement of outcomes

Emmanuel L Kuyinu et al. J Orthop Surg Res. 2016.

. 2016 Feb 2:11:19.

doi: 10.1186/s13018-016-0346-5.

Authors

Emmanuel L Kuyinu^{1

2

3}, Ganesh Narayanan^{4

5

6}, Lakshmi S Nair^{7

8

9

10

11

12}, Cato T Laurencin^{13

14

15

16

17

18

19

20}

Affiliations

¹ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. kuyinu@uchc.edu.
² Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. kuyinu@uchc.edu.
³ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. kuyinu@uchc.edu.
⁴ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. gnarayanan@uchc.edu.
⁵ Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. gnarayanan@uchc.edu.
⁶ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. gnarayanan@uchc.edu.
⁷ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. Nair@uchc.edu.
⁸ Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. Nair@uchc.edu.
⁹ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. Nair@uchc.edu.
¹⁰ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA. Nair@uchc.edu.
¹¹ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, USA. Nair@uchc.edu.
¹² Institute of Materials Science, University of Connecticut, Storrs, CT, USA. Nair@uchc.edu.
¹³ Institute for Regenerative Engineering, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
¹⁴ Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
¹⁵ Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
¹⁶ Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.
¹⁷ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.
¹⁸ Institute of Materials Science, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.
¹⁹ Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT, USA. laurencin@uchc.edu.
²⁰ Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, USA. laurencin@uchc.edu.

PMID: 26837951
PMCID: PMC4738796
DOI: 10.1186/s13018-016-0346-5

Abstract

Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort to the affected individual. Significant research is currently ongoing to understand its pathophysiology and develop successful treatment regimens based on this knowledge. Animal models have played a key role in achieving this goal. Animal models currently used to study osteoarthritis can be classified based on the etiology under investigation, primary osteoarthritis, and post-traumatic osteoarthritis, to better clarify the relationship between these models and the pathogenesis of the disease. Non-invasive animal models have shown significant promise in understanding early osteoarthritic changes. Imaging modalities play a pivotal role in understanding the pathogenesis of OA and the correlation with pain. These imaging studies would also allow in vivo surveillance of the disease as a function of time in the animal model. This review summarizes the current understanding of the disease pathogenesis, invasive and non-invasive animal models, imaging modalities, and pain assessment techniques in the animals.

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Figures

**Fig. 1**
Signaling pathways and structural changes in the development of osteoarthritis with showing the normal joint (a) and showing the diseased joint (b). *ADAMTS* a disintegrin and metalloproteinase with thrombospondin-like motifs, I interleukin, *MMP* matrix metalloproteinase, *TNF* tumor necrosis factor, *IFN* interferon, *IGF* insulin-like growth factor, *TGF* transforming growth factor, *VEGF* vascular endothelial growth factor; taken with permission from Glyn-Jones et al. [33]

**Fig. 2**
Classification of osteoarthritis models based on etiology in human equivalent being studied, primary OA and post-traumatic OA. *Dashed red box* represents the original classification of in vivo osteoarthritis models. *Blue arrows* indicate the models used to replicate the disease etiology. *Black arrows* represent the type of models used. Both non-invasive canine and lapine models involve the use of transarticular impact. OA osteoarthritis, *IATPF* intra-articular tibial plateau fracture, *CACTC* cyclic articular cartilage tibial compression

**Fig. 3**
a Non-invasive mouse models of osteoarthritis: line drawing of IATPF showing the mouse knee flexed on the cradle and indenter applying force. This causes a closed fracture of the tibial plateau. b Non-invasive mouse models of osteoarthritis: diagrammatic representation of cyclic articular cartilage tibial compression on the flexed right hind limb of the mouse. This model can also cause an ACL rupture at higher loads. The direction of the load between the upper and lower loading cups is shown. Location of strain gauges ion the apparatus (a, lateral and b, medial) on the tibial mid-shaft are also shown. *IAPF* intra-articular tibial plateau fracture, *ACL* anterior cruciate ligament. Taken with permission from Furman et al. [142] and Souza et al. [147]

**Fig. 4**
a Positioning of the beagle dog in the apparatus that was used for the application of the transarticular load. The right lower limb is held rigidly with the animal lying in lateral recumbency. Adapted with permission from Lahm et al. [157]. b Schematic representation of the experimental setup from fluoroscopy. Note the dropping tower used to apply the load on the patellofemoral joint

**Fig. 5**
Impact experiments were performed by dropping a mass with a padded impact interface (A) (3.76-MPa crush strength—Hexcel) onto the patellofemoral joint with 6.6 J of energy. Taken with permission from Ewers et al. [166]

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Animal models of osteoarthritis: classification, update, and measurement of outcomes

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