Muscle degeneration is a common issue caused by rotator cuff tear (RCT) which significantly affects prognosis. Muscle stem cells (MuSCs) play a crucial role to prevent muscle degeneration after RCT. However, the pathological changes and detailed molecular mechanism underlying the myogenesis of MuSCs after RCT remain incomplete. The current study established single-cell landscape of supraspinatus muscles and found decreased expression of PIEZO1 and impaired myogenic potential of MuSCs from RCT patients. Reduced expression of PIEZO1 impaired the myogenesis of MuSCs by inhibiting the ERK/MAPK pathways. Furthermore, selective PIEZO1 agonist Yoda1 had the potential to alleviate muscle degeneration and improve shoulder function following RCT. This study emphasized the role of PIEZO1 in the myogenesis of MuSCs and suggested that activating PIEZO1 could be a potential non-surgical treatment option to reduce muscle degeneration after RCT.
© 2024 The Author(s).

Previous studies found decreased ESR1 expression of concave paraspinal muscle progenitor cells could contribute to the initiation and progression of adolescent idiopathic scoliosis (AIS). The current study investigated the clinical characteristics of AIS with asymmetrical ESR1 expression in paraspinal muscle progenitor cells.
Bilateral deep paraspinal muscle progenitor cells were obtained from 25 consecutive eligible female patients with AIS. RT-qPCR was performed to evaluate the expression of ESR1. The demographic data (the age at surgery, height, weight, BMI, and age at initiation), posteroanterior and lateral radiographs data (Risser sign, Cobb angle, apical vertebral rotation, and location of apical vertebra), and MR imaging data (bilateral paraspinal muscle CSA ratio and bilateral fatty component ratio) were collected. The correlation between asymmetrical ESR1 expression of paraspinal muscle progenitor cells and the aforementioned clinical characteristics were analyzed.
Twelve out of twenty-five patients (48%) showed bilateral ESR1 expression ratio (convex/concave) more than 1.5 folds, and they were divided into the ESR1 asymmetry group. When compared with the ESR1 symmetry group, patients in the ESR1 asymmetry group showed significantly more severe scoliosis (p = 0.041), more hypoplastic concave paraspinal muscle (p = 0.015), and more muscular fatty infiltration in the concave side (p = 0.034). The bilateral ESR1 expression ratio was significantly correlated with Cobb angle (r 2 = 0.282, p = 0.006), bilateral paraspinal muscle CSA ratio (r 2 = 0.253, p = 0.011), and bilateral fatty component ratio (r 2 = 0.248, p = 0.011).
There were 48% of AIS patients with significantly decreased ESR1 expression in concave paraspinal muscle progenitor cells (convex/concave>1.5 folds), while patients with more asymmetrical ESR1 expression showed more hypoplastic paraspinal muscle and fatty infiltration on the concave side, and more severe scoliotic deformity.
© 2024 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

Muscular fatty infiltration is a common issue after rotator cuff tears (RCTs), which impair shoulder function. Females suffer a higher prevalence and a more severe degree of muscular fatty infiltration after RCT when compared with males, with the underlying mechanisms remaining unclear. Fibro-adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.NEW & NOTEWORTHY The current study demonstrated that gender-specific disparities in muscular fatty infiltration are attributed to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Moreover, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Therefore, metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.

Tendon injury occurs at high frequency and is difficult to repair. Identification of human stem cells being able to regenerate tendon will greatly facilitate the development of regenerative medicine for tendon injury. We identified CD29+/CD56+ human muscle stem/progenitor cells having tendon differentiation potential both in vitro and in vivo. Transplantation of human myogenic progenitor cells contributes to injured tendon repair and thus improves locomotor function. Interestingly, the tendon differentiation potential in mouse muscle stem cells is minimal and the higher TGFβ signaling level in human myogenic progenitor cells may be the key for the distinct feature of human myogenic progenitor cells. These findings reveal that CD29+/CD56+ human muscle stem/progenitor cells are bi-potential adult stem cells and can serve as a new source for tendon regeneration.

HIV-1 persists indefinitely in people living with HIV (PLWH) on antiretroviral therapy (ART). If ART is stopped, the virus rapidly rebounds from long-lived latently infected cells. Using a humanized mouse model of HIV-1 infection and CD4+ T cells from PLWH on ART, we investigate whether antagonizing host pro-survival proteins can prime latent cells to die and facilitate HIV-1 clearance. Venetoclax, a pro-apoptotic inhibitor of Bcl-2, depletes total and intact HIV-1 DNA in CD4+ T cells from PLWH ex vivo. This venetoclax-sensitive population is enriched for cells with transcriptionally higher levels of pro-apoptotic BH3-only proteins. Furthermore, venetoclax delays viral rebound in a mouse model of persistent HIV-1 infection, and the combination of venetoclax with the Mcl-1 inhibitor S63845 achieves a longer delay in rebound compared with either intervention alone. Thus, selective inhibition of pro-survival proteins can induce death of HIV-1-infected cells that persist on ART, extending time to viral rebound.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.