Lateral to medial fibro‐adipogenic degeneration are greater in infraspinatus than supraspinatus following nerve and tendon injury of murine rotator cuff

Wu, Guangjie; Hu, Vivian; McClintick, Daniel J; Gatto, Jonathan D; Aderibigbe, Temidayo; Lu, Liangyu; Jensen, Andrew R.; Dar, Ayelet; Petrigliano, Frank A.

doi:10.1002/jor.24847

Cited by 7 publications

(8 citation statements)

References 27 publications

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“…Our findings reveal that cell fate is more dominantly regulated by intrinsic properties than external signals, and that fibrogenic signaling input dominates and eliminates any degree of adipogenic differentiation when opposing pathways are simultaneously activated in fibro-adipogenic cultures. This observation is compatible with the histological analysis of degenerating RC muscles and corresponds to the presence of terminally differentiated scar populating myofibroblasts or adipose-tissue-residing mature adipocytes, but absence of cells with combined fibro-adipogenic appearances ( Jensen et al, 2018 ; Sharma et al, 2020 ; Wu et al, 2021 ).…”

Section: Discussionsupporting

confidence: 88%

Distinct human skeletal muscle-derived CD90 progenitor subsets for myo-fibro-adipogenic disease modeling and treatment in multiplexed conditions

Anbuchelvan

Fathi

et al. 2023

Front. Cell Dev. Biol.

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Chronic muscle injuries, such as massive rotator cuff tears, are associated with progressive muscle wasting, fibrotic scarring, and intramuscular fat accumulation. While progenitor cell subsets are usually studied in culture conditions that drive either myogenic, fibrogenic, or adipogenic differentiation, it is still unknown how combined myo-fibro-adipogenic signals, which are expected to occur in vivo, modulate progenitor differentiation. We therefore evaluated the differentiation potential of retrospectively generated subsets of primary human muscle mesenchymal progenitors in multiplexed conditions in the presence or absence of 423F drug, a modulator of gp130 signaling. We identified a novel CD90+CD56− non-adipogenic progenitor subset that maintained a lack of adipogenic potential in single and multiplexed myo-fibro-adipogenic culture conditions. CD90−CD56− demarcated fibro-adipogenic progenitors (FAP) and CD56+CD90+ progenitors were typified as myogenic. These human muscle subsets exhibited varying degrees of intrinsically regulated differentiation in single and mixed induction cultures. Modulation of gp130 signaling via 423F drug mediated muscle progenitor differentiation in a dose-, induction-, and cell subset-dependent manner and markedly decreased fibro-adipogenesis of CD90−CD56− FAP. Conversely, 423F promoted myogenesis of CD56+CD90+ myogenic subset, indicated by increased myotube diameter and number of nuclei per myotube. 423F treatment eliminated FAP-derived mature adipocytes from mixed adipocytes-FAP cultures but did not modify the growth of non-differentiated FAP in these cultures. Collectively, these data demonstrate that capability of myogenic, fibrogenic, or adipogenic differentiation is largely dependent on the intrinsic features of cultured subsets, and that the degree of lineage differentiation varies when signals are multiplexed. Moreover, our tests performed in primary human muscle cultures reveal and confirm the potential triple-therapeutic effects of 423F drug which simultaneously attenuates degenerative fibrosis, fat accumulation and promotes myo-regeneration.

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Section: Discussionsupporting

confidence: 88%

Distinct human skeletal muscle-derived CD90 progenitor subsets for myo-fibro-adipogenic disease modeling and treatment in multiplexed conditions

Anbuchelvan

Fathi

et al. 2023

Front. Cell Dev. Biol.

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“…FAP-specific activation state may also affect cell behaviour response to vorinostat, and our study shows that the supraspinatus and infraspinatus muscles were not equally affected by the injury procedure, as previously demonstrated by others. 28 Moreover, injury disease stage may further explain why the benefits of vorinostat treatment after RC injury decrease over time. Preclinical studies in muscular disorders indicate that the beneficial effects of the pan-HDACi trichostatin A are restricted to early stages of disease.…”

Section: Discussionmentioning

confidence: 99%

“… 39 Although spontaneous healing of supraspinatus and infraspinatus tendons after transection can occur, it does not prevent muscle degeneration occurring after RC injury. 28 , 40 Notably, our study did not include long-term stages of RC injury, during which muscular fatty infiltration becomes more prominent. Our research was focused on the hypothesis that vorinostat plays a role in early-to-middle stage of RC injury, when there is observable evidence of degenerative changes in the supraspinatus and infraspinatus muscles, which are preceded by an inflammatory peak response.…”

Section: Discussionmentioning

confidence: 99%

HDACi vorinostat protects muscle from degeneration after acute rotator cuff injury in mice

Gil-Melgosa,

Llombart-Blanco,

Extramiana

et al. 2024

Bone Joint Res

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AimsRotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.MethodsHDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.ResultsVorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy.ConclusionThe HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury.Cite this article: Bone Joint Res 2024;13(4):169–183.

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“…Furthermore, IL-10 concentrations increase in muscle, decreasing myofiber injury, when regulatory T cells increase [ 46 ]. Our data showed up-regulation of IL-10 mRNA level in tibialis anterior injected with nitric oxide was detected on notexin-induced muscle damage [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Protective action of ultrasound-guided electrolysis technique on the muscle damage induced by notexin in rats

et al. 2022

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It is known that exercise can be one of the causes of muscular damage. In recent times, physiotherapists and medical professionals have been employing USGET techniques to stimulate muscle recovery to improve its performance after the injury. We pretend to analyse if the Ultrasound-guided electrolysis (USGET) technique could reduce muscle damage, inflammation, and pain in the present study. Female Wistar rats were assigned to one of three different groups: control (C), notexin (NOT) and notexin with USGET (electrolysis at 6mA) (NOT+USGET). We used the USGT technique, based on electrical stimulation with a continuous current of 4 pulses at an intensity of 6 mA for 5 seconds, conveyed to the muscle. The response was tested with motor function tests. In these tests, we could observe an increase in time and foot faults when crossing a beam in the NOT group compared to C group rats. On the other hand, a significant decrease in both variables was detected in the NOT+USGET compared to the NOT group. Muscle power was measured with a grip strength test, obtaining far better performances in NOT+USGET rats when compared to NOT rats. Moreover, the USGET technique prevented the increase of pro-inflammatory proteins IL-6 and chemokines CCL3 (Chemokine (C-C motif) ligand 3), CCL4 (Chemokine (C-C motif) ligand 4), and CCL5 (Chemokine (C-C motif) ligand 5) with their receptor CCR5 (C-C chemokine receptor type 5), induced by notexin in the quadriceps. At the same time, the study evidenced a decrease in both CCR8 (C-C chemokine receptor type 5,) and NF-ᴋB (nuclear factor- ᴋB) expressions after USGET treatment. On the other hand, we obtained evidence that demonstrated anti-inflammatory properties of the USGET technique, thus being the increase in IL-10 (Interleukin 10) and IL-13 (Interleukin 13) in the NOT+USGET group compared to the NOT group. Furthermore, when applying NSGET after damage, an increase in anti-inflammatory mediators and reduction of pro-inflammatory mediators, which, overall, promoted muscle regeneration, was observed. These results support the idea that the NSGET technique improves muscle recovery after toxic damages, which would justify its employment.

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Lateral to medial fibro‐adipogenic degeneration are greater in infraspinatus than supraspinatus following nerve and tendon injury of murine rotator cuff

Cited by 7 publications

References 27 publications

Distinct human skeletal muscle-derived CD90 progenitor subsets for myo-fibro-adipogenic disease modeling and treatment in multiplexed conditions

Distinct human skeletal muscle-derived CD90 progenitor subsets for myo-fibro-adipogenic disease modeling and treatment in multiplexed conditions

HDACi vorinostat protects muscle from degeneration after acute rotator cuff injury in mice

Protective action of ultrasound-guided electrolysis technique on the muscle damage induced by notexin in rats

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