Effect of hypercholesterolemia on fatty infiltration and the quality of tendon-to-bone healing in a rabbit model of a chronic rotator cuff tear: Electrophysiological, biomechanical, and histological analyses

Background: The infiltration of fat tissue into skeletal muscle, a condition referred to as muscle fatty infiltration or fatty degeneration, is regarded as an irreversible event that significantly compromises the motor function of skeletal muscle. Purpose: To investigate the effect of retinoic acid receptor (RAR) agonists in suppressing the adipogenic differentiation of fibroadipogenic progenitors (FAPs) in vitro and fatty infiltration after rotator cuff tear in mice. Study Design: Controlled laboratory study. Methods: FAPs isolated from mouse skeletal muscle were cultured in adipogenic differentiation medium in the presence or absence of an RAR agonist. At the end of cell culture, adipogenic differentiation was evaluated by gene expression analysis and oil red O staining. A mouse model of fatty infiltration—which includes the resection of the rotator cuff, removal of the humeral head, and denervation the supraspinatus muscle—was used to induce fatty infiltration in the supraspinatus muscle. The mice were orally or intramuscularly administered with an RAR agonist after the surgery. Muscle fatty infiltration was evaluated by histology and gene expression analysis. Results: RAR agonists effectively inhibited the adipogenic differentiation of FAPs in vitro. Oral and intramuscular administration of RAR agonists suppressed the development of muscle fatty infiltration in the mice after rotator cuff tear. In accordance, we found a significant decrease in the number of intramuscular fat cells and suppressed expression in adipogenic markers. RAR agonists also increased the expression of the transcripts for collagens; however, an accumulation of collagenous tissues was not histologically evident in the present model. Conclusion: Muscle fatty infiltration can be alleviated by RAR agonists through suppressing the adipogenic differentiation of FAPs. The results also suggest that RAR agonists are potential therapeutic agents for treating patients who are at risk of developing muscle fatty infiltration. The consequence of the increased expression of collagen transcripts by RAR agonists needs to be clarified. Clinical Relevance: RAR agonists can be used to prevent the development of muscle fatty infiltration after rotator cuff tear. Nevertheless, further studies are mandatory in a large animal model to examine the safety and efficacy of intramuscular injection of RAR agonists.

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Fatty acid-binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia-inducible factor 1 in mice

Journal of Cachexia Sarcopenia and Muscle ◽

10.1002/jcsm.12203 ◽

2017 ◽

Vol 8 (5) ◽

pp. 839-850 ◽

Cited By ~ 10

Author(s):

Yong-Soo Lee ◽

Ja-Yeon Kim ◽

Kyung-Soo Oh ◽

Seok Won Chung

Keyword(s):

Fatty Acid ◽

Rotator Cuff ◽

Rotator Cuff Tear ◽

Fatty Acid Binding Protein ◽

Fatty Infiltration ◽

Hypoxia Inducible Factor ◽

Fatty Acid Binding ◽

Hypoxia Inducible Factor 1 ◽

Acid Binding Protein ◽

Cuff Tear

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Into-Tunnel Repair Versus Onto-Surface Repair for Rotator Cuff Tears in a Rabbit Model

The American Journal of Sports Medicine ◽

10.1177/0363546518764685 ◽

2018 ◽

Vol 46 (7) ◽

pp. 1711-1719 ◽

Cited By ~ 8

Author(s):

Xiaoxi Li ◽

Peng Shen ◽

Wei Su ◽

Song Zhao ◽

Jinzhong Zhao

Keyword(s):

Rotator Cuff ◽

Rotator Cuff Tear ◽

Bone Healing ◽

Surface Group ◽

The Other ◽

Rotator Cuff Tears ◽

Bone Interface ◽

Cuff Tear ◽

Retear Rate ◽

Surface Repair

Background: Clinically, onto-surface repair is commonly used for rotator cuff tears. The retear rate after rotator cuff repair (RCR) is relatively high, with failure occurring mostly at the tendon-bone connection site. For anterior cruciate ligament (ACL) reconstruction, into-tunnel reconstruction is commonly employed. The retear rate after ACL reconstruction is relatively low, with retears seldom occurring at the tendon-bone interface. No study on into-tunnel RCR has been conducted. Hypothesis: Into-tunnel RCR could promote fibrocartilage regeneration at the tendon-bone interface and has biomechanical advantage over onto-surface repair in a rabbit rotator cuff tear model. Study Design: Controlled laboratory study. Methods: Thirty-six New Zealand White rabbits were used in this study. The supraspinatus tendons were cut from the footprint to create a rotator cuff tear on both shoulders. On one side, the supraspinatus was cut longitudinally into 2 halves, sutured, and pulled into 2 tunnels through the greater tuberosity (into-tunnel repair). On the other side, the tendon was reattached to the surface of the footprint with transosseous sutures (onto-surface repair). Twelve animals were sacrificed, of which 6 were used for a histological examination and the other 6 for biomechanical testing, at 4, 8, and 12 weeks, respectively. Results: The tendon-bone interface in the into-tunnel group showed a different healing pattern from that in the onto-surface group. In the former, most of the tendon tissue in the tunnel was replaced with newly generated fibrocartilage; the rest of the tendon fibers appeared in large bundles with direct connection to the bone. In the latter, fibrocartilage regeneration was seldom found at the tendon-bone interface; the tendon near the bone surface appeared as small fibrils. The biomechanical evaluation revealed a higher ultimate load ( P < .001) and stiffness ( P < .001) at the tendon-bone junction in the into-tunnel group than those in the onto-surface group at 12 weeks. Conclusion: In a rabbit rotator cuff tear model, into-tunnel RCR could result in a different tendon-bone healing pattern, with obvious fibrocartilage regeneration at the interface and higher tendon-bone healing strength than that in onto-surface repair. Clinical Relevance: New RCR patterns may be developed to improve the tendon-bone healing pattern and obtain better tendon-bone healing strength.

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