Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator cuff tears using continuous musculotendinous traction. An experimental study in sheep

Gerber, Christian; Meyer, Dominik C.; Frey, Eric; Rechenberg, Brigitte von; Hoppeler, Hans; Frigg, R.; Jost, Bernhard; Zumstein, Matthias A.

doi:10.1016/j.jse.2008.09.003

Cited by 139 publications

(132 citation statements)

References 37 publications

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“…Interestingly, the mRNA level of Fabp3 , the muscle type of FABP,37 showed no noticeable change ( Figure 2b). In general, RCT causes profound changes in muscles such as fatty infiltration, muscle degeneration, and atrophy 38. To validate our mouse RCT model, we analysed the expression of several genes associated with inflammation, adipogenesis, and myogenesis.…”

Section: Resultsmentioning

confidence: 99%

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

Lee

Kim

et al. 2017

J cachexia sarcopenia muscle

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BackgroundFatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid‐binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model.MethodsIn the RCT model, we evaluated the expression of FABP4 by qRT‐PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia‐inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively.ResultsFABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear‐induced FABP4 expression was up‐regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter activity of FABP4, together with HIF1β. Hypoxia‐induced FABP4 expression was significantly decreased by HIF1 inhibitor treatment. Furthermore, in RCT model mice, fat accumulation was remarkably reduced by FABP4 inhibitor treatment.ConclusionsThis study shows that RCT induces FABP4 expression, leading to fat accumulation in injured muscle. FABP4 transcription is regulated by the direct binding of HIF1 to the FABP4 promoter in the hypoxic condition induced by RCT. Fat accumulation in injured muscle was reduced by the inhibition of FABP4. Ultimately, in the RCT model, we identified a novel mechanism for fatty infiltration by FABP4, which differs from adipogenic differentiation of muscle stem cells, and we found that fatty infiltration might be regulated by inhibition of HIF1 or FABP4.

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Section: Resultsmentioning

confidence: 99%

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

Lee

Kim

et al. 2017

J cachexia sarcopenia muscle

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“…T he structural and functional alterations of the musculotendinous unit as a consequence of chronic tendon tears are considered irreversible on direct tendon repair and have been shown to be partly reversible with continuous relengthening of the retracted myotendinous unit 10 . It is desirable to inhibit the development of these changes in the first place.…”

Section: Discussionmentioning

confidence: 99%

“…histomorphometry by a blinded observer, as described previously 5,10 , by coloring four different phases with a software program (Adobe Photoshop 7; Adobe Systems, San Jose, California). The background, representing empty space on the histological sections, was subtracted before calculation of the proportional amounts of fat, muscle, and fibrosis.…”

Section: Imaging and Histological Evaluationsmentioning

confidence: 99%

“…To date, full anatomical and functional restoration of a deteriorated musculotendinous unit has not been achieved. Continuous relengthening experimentally restored architectural changes caused by chronic rotator cuff tearing in a sheep model 10 ; fibrosis and atrophy of the muscle were halted and partially reversed by continuous traction and staged repair, but fatty infiltration could not be reversed either experimentally or clinically. New strategies for the prevention, or at least the reduction, of muscle degeneration are of substantial interest.…”

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confidence: 92%

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Anabolic Steroids Reduce Muscle Damage Caused by Rotator Cuff Tendon Release in an Experimental Study in Rabbits

Gerber

Meyer

Nuss

et al. 2011

Journal of Bone and Joint Surgery

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To our knowledge, this is the first documentation of partial prevention of important muscle alterations after retraction of the supraspinatus musculotendinous unit caused by tendon disruption. Nandrolone decanoate administration in the phase after tendon release prevented fatty infiltration of the supraspinatus muscle and reduced functional muscle impairment caused by myotendinous retraction in this rabbit rotator cuff model, but two of seven rabbits that received the drug developed infections. Background: Muscles of the rotator cuff undergo retraction, atrophy, and fatty infiltration after a chronic tear, and a rabbit

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“…Animal models of RC tears with FI have demonstrated decreased tendon mechanical properties (8). Gerber et al demonstrated in an ovine model that detachment and retraction of infraspinatus muscles resulted in a significant increase in FI and decreased cross-sectional area (9). Traction was then applied to increase the muscletendon unit length following RC repair, which prevented progression of fatty changes.…”

Section: Pathophysiology Of Fimentioning

confidence: 99%

Role of fatty infiltration in the pathophysiology and outcomes of rotator cuff tears

Chaudhury

Dines

Delos

et al. 2011

Arthritis Care & Research

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Neer Award 2007: Reversion of structural muscle changes caused by chronic rotator cuff tears using continuous musculotendinous traction. An experimental study in sheep

Cited by 139 publications

References 37 publications

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

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

Anabolic Steroids Reduce Muscle Damage Caused by Rotator Cuff Tendon Release in an Experimental Study in Rabbits

Role of fatty infiltration in the pathophysiology and outcomes of rotator cuff tears

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