Myofiber androgen receptor increases muscle strength mediated by a skeletal muscle splicing variant of Mylk4

Sakakibara, Iori; Yanagihara, Yoshio; Himori, Koichi; Yamada, Takashi; Sakai, Hiroshi; Sawada, Yuichiro; Takahashi, Hirotaka; Saeki, Noritaka; Hirakawa, Hiromasa; Yokoyama, Atsushi; Fukada, So Ichiro; Sawasaki, Tatsuya; Imai, Yuuki

doi:10.1016/j.isci.2021.102303

Cited by 28 publications

(29 citation statements)

References 34 publications

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“…These polyamine synthetic genes were previously shown to be male enriched and androgen inducible 14 , 15 , 17 , 27 . As for their function in skeletal muscles, they were reported to suppress muscle atrophy and promote hypertrophy 29 , 30 , possibly by regulating cellular proliferation and viability 31 , 32 as well as protein synthesis 33 and autophagy 34 , 35 .…”

Section: Resultsmentioning

confidence: 92%

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Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle

et al. 2021

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Skeletal muscles display sexually dimorphic features. Biochemically, glycolysis and fatty acid β-oxidation occur preferentially in the muscles of males and females, respectively. However, the mechanisms of the selective utilization of these fuels remains elusive. Here, we obtain transcriptomes from quadriceps type IIB fibers of untreated, gonadectomized, and sex steroid-treated mice of both sexes. Analyses of the transcriptomes unveil two genes, Pfkfb3 (phosphofructokinase-2) and Pdk4 (pyruvate dehydrogenase kinase 4), that may function as switches between the two sexually dimorphic metabolic pathways. Interestingly, Pfkfb3 and Pdk4 show male-enriched and estradiol-enhanced expression, respectively. Moreover, the contribution of these genes to sexually dimorphic metabolism is demonstrated by knockdown studies with cultured type IIB muscle fibers. Considering that skeletal muscles as a whole are the largest energy-consuming organs, our results provide insights into energy metabolism in the two sexes, during the estrus cycle in women, and under pathological conditions involving skeletal muscles.

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Section: Resultsmentioning

confidence: 92%

“…1c ). Amd (S-adenosylmethionine decarboxylase) and Smox (spermine oxidase), both of which are required for polyamine synthesis, were reported to exhibit male-enriched and androgen-induced expression 14 , 15 , 17 , 27 . The expressions of these genes were examined in quadriceps type IIB fibers.…”

Section: Resultsmentioning

confidence: 99%

Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle

et al. 2021

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“…In a study using depletion of satellite cells and testosterone treatment, it was discovered that muscle hypertrophy occurred in testosterone-treated female mice regardless if the mice were depleted with SC (Pax7 CreER/CreER +;Rosa26 DTA/DTA ) or with the normal number of SC (38). This was further confirmed when satellite cell-specific AR KO (Pax7 CreERT2 +;AR flox )female mice exhibited increased mass upon testosterone treatment (39). In the same study, a myofiber-specific ArKO or mArKO (Ar flox/flox ; HSA-Cre) was observed to have increased muscle mass upon testosterone treatment while there was a loss in grip strength.…”

Section: Androgen Effects On Muscle Developmentmentioning

confidence: 93%

“…This indicates that muscle mass is not controlled by AR in the myofiber or satellite cell but muscle strength is directly affected by androgen signaling. An RNA seq of the mARKO suggests that glucose/amino acid metabolism and muscle sarcomeric gene regulation, such as Mylk4 , is regulated by androgen signaling ( 39 ).…”

Section: Androgen Effects On Muscle Developmentmentioning

confidence: 99%

Sexual dimorphism through androgen signaling; from external genitalia to muscles

Ipulan-Colet

2022

Front. Endocrinol.

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Sexual dimorphisms can be seen in many organisms with some exhibiting subtle differences while some can be very evident. The difference between male and female can be seen on the morphological level such as discrepancies in body mass, presence of body hair in distinct places, or through the presence of specific reproductive structures. It is known that the development of the reproductive structures is governed by hormone signaling, most commonly explained through the actions of androgen signaling. The developmental program of the male and female external genitalia involves a common anlage, the genital tubercle or GT, that later on develop into a penis and clitoris, respectively. Androgen signaling involvement can be seen in the different tissues in the GT that express Androgen receptor and the different genes that are regulated by androgen in the mesenchyme and endoderm component of the GT. Muscles are also known to be responsive to androgen signaling with male and female muscles exhibiting different capabilities. However, the occurrence of sexual dimorphism in muscle development is unclear. In this minireview, a summary on the role of androgen in the sexually dimorphic development of the genital tubercle was provided. This was used as a framework on analyzing the different mechanism employed by androgen signaling to regulate the sexual dimorphism in muscle development.

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“…Total RNA-seq was performed as described previously 43 – 45 . The integrity of the isolated RNA was verified using the 2100 Bioanalyzer (Agilent Technologies).…”

Section: Methodsmentioning

confidence: 99%

Reduced dynamic loads due to hip dislocation induce acetabular cartilage degeneration by IL-6 and MMP3 via the STAT3/periostin/NF-κB axis

Nakamura

Saitou

Komura

et al. 2022

Sci Rep

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Developmental dysplasia of the hip (DDH) is characterized by anatomical abnormalities of the hip joint, ranging from mild acetabular dysplasia to hip subluxation and eventually dislocation. The mechanism underlying the cartilage degeneration of the hip joints exposed to reduced dynamic loads due to hip dislocation remains unknown. We established a rodent hip dislocation (disarticulation; DA) model of DDH (DA-DDH rats and mice) by swaddling. Expression levels of periostin (Postn) and catabolic factors, such as interleukin-6 (IL-6) and matrix metalloproteinase 3 (Mmp3), increased and those of chondrogenic markers decreased in the acetabular cartilage of the DA-DDH models. Postn induced IL-6 and Mmp3 expression in chondrocytes through integrin αVβ3, focal adhesion kinase, Src, and nuclear factor-κB (NF-κB) signaling. The microgravity environment created by a random positioning machine induced Postn expression in chondrocytes through signal transducer and activator of transcription 3 (STAT3) signaling. IL-6 stimulated Postn expression via STAT3 signaling. Furthermore, cartilage degeneration was suppressed in the acetabulum of Postn−/− DA-DDH mice compared with that in the acetabulum of wild type DA-DDH mice. In summary, reduced dynamic loads due to hip dislocation induced acetabular cartilage degeneration via IL-6 and MMP3 through STAT3/periostin/NF-κB signaling in the rodent DA-DDH models.

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Myofiber androgen receptor increases muscle strength mediated by a skeletal muscle splicing variant of Mylk4

Cited by 28 publications

References 34 publications

Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle

Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle

Sexual dimorphism through androgen signaling; from external genitalia to muscles

Reduced dynamic loads due to hip dislocation induce acetabular cartilage degeneration by IL-6 and MMP3 via the STAT3/periostin/NF-κB axis

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