Development of a novel animal model of rotator cuff tear arthropathy replicating clinical features of progressive osteoarthritis with subchondral bone collapse

T Ijuin; T Iuchi; H Tawaratsumida; Y Masuda; A Tokushige; S Maeda; N Taniguchi

doi:10.1016/j.ocarto.2023.100389

Development of a novel animal model of rotator cuff tear arthropathy replicating clinical features of progressive osteoarthritis with subchondral bone collapse

Osteoarthr Cartil Open. 2023 Jul 27;5(3):100389. doi: 10.1016/j.ocarto.2023.100389. eCollection 2023 Sep.

Authors

T Ijuin^{1

2}, T Iuchi¹, H Tawaratsumida¹, Y Masuda^{1

3}, A Tokushige⁴, S Maeda⁵, N Taniguchi^{1

2

3

5}

Affiliations

¹ Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima 890-8520, Japan.
² Department of Medical Joint Materials, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima 890-8520, Japan.
³ Department of Locomotory Organ Regeneration, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima 890-8520, Japan.
⁴ Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Nakagami Gun Nishihara Cho, Okinawa 903-0213, Japan.
⁵ Department of Bone and Joint Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima 890-8520, Japan.

Abstract

Objective: To establish an animal model of modified cuff tear arthropathy (mCTA) in order to better replicate the pathophysiology associated with rotator cuff tear-induced humeral head collapse.

Design: mCTA was induced by transection of the rotator cuff, the long head of the biceps brachii (LHB), and superior half of the joint capsule in the right shoulder of 12-week-old rats; the left shoulder underwent sham surgery. The severity of CTA was quantitated using the Murine Shoulder Arthritis Score (MSAS). The trabecular bone of the humeral head and metaphysis was analyzed using bone histomorphometry. The expression of proinflammatory cytokines and catabolic enzymes was evaluated immunohistochemically.

Results: In the mCTA model, the MSAS increased starting from 2 weeks after induction, and there was notable subchondral bone collapse with fibrous cells at 4 weeks. The mCTA cartilage exhibited positive staining for TNF-α, IL-1β/6, MMP-3/13, and ADAMTS5. The trabecular bone volume was reduced not only in the subchondral bone but also in the metaphysis of the humeri, and bone resorption was enhanced in these areas. In the collapsed subchondral bone, both bone formation and resorption were increased. The fibrous cells showed expression of TNF-α, IL-6, and MMP-13, along with specific markers of mesenchymal stem cells. Furthermore, the fibrous cells showed osteoblastic characteristics (RUNX2-positive) and expressed RANKL.

Conclusions: The LHB and the capsuloligamentous complex are critical stabilizers of the glenohumeral joint, serving to prevent the advancement of CTA following massive rotator cuff tears. Fibrous cells appear to play a role in the humeral head bone resorption.

Keywords: Capsuloligamentous complex; Cuff tear arthropathy; Fibrous cells; Long head of biceps; Osteoarthritis; Subchondral bone collapse.