Identification of gravity-responsive proteins in the femur of spaceflight mice using a quantitative proteomic approach

Egashira, Kenji; Ino, Yoko; Nakai, Yoshikazu; Ohira, Takashi; Akiyama, Tomoko; Moriyama, Kayano; Yamamoto, Yu; Kimura, Mitsuo; Ryo, Akihide; Saito, T.; Inaba, Yutaka; Hirano, Hisashi; Kumagai, Ken; Kimura, Yayoi

doi:10.1016/j.jprot.2023.104976

Cited by 3 publications

(4 citation statements)

References 47 publications

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“…PCA suggested that gravity differences distinguished the sample groups more obviously than the presence or absence of FOS intake (Figure S1A). Although FOSs have been shown to increase bone mass in growing rats [25], FOS intake did not affect bone mass [21] or the absolute wet weight of the soleus or extensor digitorum longus muscle [22] in the spaceflight mice used in our experiment. Therefore, in this study, we compared serum proteome profiles between μ-g and A1-g environments without distinguishing between FOS intake.…”

Section: Discovery Of Mouse Serum Proteins Differentially Expressed I...contrasting

confidence: 56%

“…MARS allows us to compare the biological effects of μ-g and A1-g on mice raised in different gravity environments in space, making it possible to evaluate the systemic effects of physical inactivity [17,18]. The effects of μ-g exposure on the retina [19], thymus [20], femur [21], and skeletal muscle [22,23], but not serum, of spaceflight mice bred using MARS have already been analyzed using proteomic and transcriptomic approaches, which showed that protein and gene expression of these tissues were influenced by gravitational unloading. On the other hand, our previous MS-based proteomic analysis of spaceflight mice could not rule out the possibility that gravity reloading after return to Earth affected protein expression in the soleus muscle [22].…”

Section: Significance Statementmentioning

confidence: 99%

“…Furthermore, comparing serum proteomic data between spaceflight and HU mice allowed for the identification of serum proteins that exhibit physiological changes induced by gravity unloading. We also collectively evaluated proteomic data from the serum, femur [21],…”

Section: Significance Statementmentioning

confidence: 99%

“…In a previous study, we obtained proteomic data for the femur [21] and soleus muscle [22,23] of the same spaceflight mice as those used in this study. To ascertain the relationships between protein level changes in serum, femur, and soleus muscle during prolonged spaceflight missions, we collectively evaluated the proteomic data from all three sources in TA B L E 2 List of proteins with similar level changes (p value [-log 10 ] > 1.3) in the serum, soleus muscle, and femur of spaceflight mice with μ-g versus A1-g exposure.…”

Section: Identification Of Bone-and Muscle-related Mouse Serum Protei...mentioning

confidence: 99%

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Identification of gravity‐responsive serum proteins in spaceflight mice using a quantitative proteomic approach with data‐independent acquisition mass spectrometry

Kimura,

Nakai,

Ino

et al. 2024

Proteomics

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Physical inactivity associated with gravity unloading, such as microgravity during spaceflight and hindlimb unloading (HU), can cause various physiological changes. In this study, we attempted to identify serum proteins whose levels fluctuated in response to gravity unloading. First, we quantitatively assessed changes in the serum proteome profiles of spaceflight mice using mass spectrometry with data‐independent acquisition. The serum levels of several proteins involved in the responses to estrogen and glucocorticoid, blood vessel maturation, osteoblast differentiation, and ossification were changed by microgravity exposure. Furthermore, a collective evaluation of serum proteomic data from spaceflight and HU mice identified 30 serum proteins, including Mmp2, Igfbp2, Tnc, Cdh5, and Pmel, whose levels varied to a similar extent in both gravity unloading models. These changes in serum levels could be involved in the physiological changes induced by gravity unloading. A collective evaluation of serum, femur, and soleus muscle proteome data of spaceflight mice also showed 24 serum proteins, including Igfbp5, Igfbp3, and Postn, whose levels could be associated with biological changes induced by microgravity. This study examined serum proteome profiles in response to gravity unloading, and may help deepen our understanding of microgravity adaptation mechanisms during prolonged spaceflight missions.

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Section: Discovery Of Mouse Serum Proteins Differentially Expressed I...contrasting

confidence: 56%

Section: Significance Statementmentioning

confidence: 99%

Section: Significance Statementmentioning

confidence: 99%

Section: Identification Of Bone-and Muscle-related Mouse Serum Protei...mentioning

confidence: 99%

See 2 more Smart Citations

Identification of gravity‐responsive serum proteins in spaceflight mice using a quantitative proteomic approach with data‐independent acquisition mass spectrometry

Kimura,

Nakai,

Ino

et al. 2024

Proteomics

Self Cite

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F‐actin microfilaments affect the LIPUS‐promoted osteogenic differentiation of BMSCs through TRPM7

Yao,

Tang,

Wang

et al. 2024

Biotechnology Journal

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The differentiation of bone marrow mesenchymal stem cells (BMSCs) toward osteogenesis can be induced by low‐intensity pulsed ultrasound (LIPUS). However, the molecular mechanisms responsible for LIPUS stimulation are unclear. The possible molecular mechanisms by which LIPUS promotes osteogenic differentiation of BMSCs were investigated in this study. The quantification of alkaline phosphatase (ALP) activity, Alizarin Red S staining, ALP staining, and the establishment of a calvarial defect model were used to evaluate osteogenic effects. Immunofluorescence was performed to observe the expression of microfilaments and transient receptor potential melastatin 7 (TRPM7). The levels of F‐actin/G‐actin and osteogenesis‐related proteins under LIPUS alone or LIPUS combined with cytoskeleton interfering drugs (Cytochalasin D [CytoD] or Jasplakinolide [JA]) were assayed by western blot. Quantitative real‐time reverse transcription polymerase chain reaction was utilized to measure the expression of Trpm7 mRNA. Moreover, adenoviral Trpm7 knockdown was verified using western blot. The results demonstrated that LIPUS promoted bone formation in vivo. Under osteogenic induction in vitro, the osteogenesis of BMSCs induced by LIPUS was accompanied by the depolymerization and rearrangement of microfilaments and increased levels of TRPM7. By perturbing intracellular actin dynamics, CytoD enhanced the pro‐osteogenicity of LIPUS and increased TRPM7 level, while JA inhibited the pro‐osteogenicity of LIPUS and reduced TRPM7 level. Additionally, the knockdown of Trpm7 suppressed the osteogenic promotion of BMSCs induced by LIPUS. The transient depolymerization and rearrangement of the cytoskeleton microfilaments mediated by LIPUS can affect TRPM7 expression and subsequently promote the osteogenesis of BMSCs. This study provides further direction for exploring the molecular mechanism of LIPUS, as a mechanical stress, in facilitating the osteogenic differentiation of BMSCs.

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Microgravity’s effects on miRNA-mRNA regulatory networks in a mouse model of segmental bone defects

Gautam,

Chakraborty,

Dimitrov

et al. 2024

PLoS ONE

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Rehabilitation from musculoskeletal injuries (MSKI) complicate healing dynamics typically by sustained disuse of bone and muscles. Microgravity naturally allows limb disuse and thus an effective model to understand MSKI. The current study examined epigenetic changes in a segmental bone defect (SBD) mouse model in a prolonged unloading condition after spaceflight (FLT). We further connected potential miRNA–mRNA regulatory pathways impacting bone healing. Here, SBD surgery was performed on nine-week-old male mice that were launched into space for approximately 4 weeks. Sham with no surgery and ground controls were included in the study. The midshaft of the ipsilateral femur (with callus on the surgical mice) as well as the ipsilateral quadriceps tissue were used for analysis. Femur and quadriceps had a distinct miRNA profile. There was a stronger surgery effect as observed by miRNA expression when compared to microgravity effects. Leukopoiesis, granulopoiesis, myelopoiesis of leukocytes, differentiation of myeloid leukocytes, and differentiation of progenitor cells were all altered because of surgery in the femur. The biological functions such as apoptosis, necrosis, and activation of cell migration and viability were altered because of surgery in quadriceps. Integrating the transcriptome and microRNA data indicated pronounced changes because of microgravity. According to pathway analysis, microgravity had a greater impact on the quadriceps tissue than the bone tissue in the absence of surgery. The altered biological functions resulting from microgravity were validated by integrating limited proteomics data to miRNA-mRNA. Thus, this study highlights the importance of dynamic interplay of gene-epigene regulations as they appear to be intrinsically interconnected and influence in combination for the biological outcome.

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Identification of gravity-responsive proteins in the femur of spaceflight mice using a quantitative proteomic approach

Cited by 3 publications

References 47 publications

Identification of gravity‐responsive serum proteins in spaceflight mice using a quantitative proteomic approach with data‐independent acquisition mass spectrometry

Identification of gravity‐responsive serum proteins in spaceflight mice using a quantitative proteomic approach with data‐independent acquisition mass spectrometry

F‐actin microfilaments affect the LIPUS‐promoted osteogenic differentiation of BMSCs through TRPM7

Microgravity’s effects on miRNA-mRNA regulatory networks in a mouse model of segmental bone defects

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