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Effects of pleiotrophin overexpression on mouse skeletal muscles in normal loading and in actual and simulated microgravity.

Camerino GM, Pierno S, Liantonio A, De Bellis M, Cannone M, Sblendorio V, Conte E, Mele A, Tricarico D, Tavella S, Ruggiu A, Cancedda R, Ohira Y, Danieli-Betto D, Ciciliot S, Germinario E, Sandonà D, Betto R, Camerino DC, Desaphy JF - PLoS ONE (2013)

Bottom Line: PTN overexpression did not prevent soleus muscle atrophy, slow-to-fast transition, and capillary regression induced by SF and HU.The numerous effects of PTN on muscle gene expression and functional parameters demonstrate the sensitivity of muscle fibers to the cytokine.Although little benefit was found in HU muscle disuse, PTN may emerge useful in various muscle diseases, because it exerts synergetic actions on muscle fibers and vessels, which could enforce oxidative metabolism and ameliorate muscle performance.

View Article: PubMed Central - PubMed

Affiliation: Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari, Italy.

ABSTRACT
Pleiotrophin (PTN) is a widespread cytokine involved in bone formation, neurite outgrowth, and angiogenesis. In skeletal muscle, PTN is upregulated during myogenesis, post-synaptic induction, and regeneration after crushing, but little is known regarding its effects on muscle function. Here, we describe the effects of PTN on the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles in mice over-expressing PTN under the control of a bone promoter. The mice were maintained in normal loading or disuse condition, induced by hindlimb unloading (HU) for 14 days. Effects of exposition to near-zero gravity during a 3-months spaceflight (SF) into the Mice Drawer System are also reported. In normal loading, PTN overexpression had no effect on muscle fiber cross-sectional area, but shifted soleus muscle toward a slower phenotype, as shown by an increased number of oxidative type 1 fibers, and increased gene expression of cytochrome c oxidase subunit IV and citrate synthase. The cytokine increased soleus and EDL capillary-to-fiber ratio. PTN overexpression did not prevent soleus muscle atrophy, slow-to-fast transition, and capillary regression induced by SF and HU. Nevertheless, PTN exerted various effects on sarcolemma ion channel expression/function and resting cytosolic Ca(2+) concentration in soleus and EDL muscles, in normal loading and after HU. In conclusion, the results show very similar effects of HU and SF on mouse soleus muscle, including activation of specific gene programs. The EDL muscle is able to counterbalance this latter, probably by activating compensatory mechanisms. The numerous effects of PTN on muscle gene expression and functional parameters demonstrate the sensitivity of muscle fibers to the cytokine. Although little benefit was found in HU muscle disuse, PTN may emerge useful in various muscle diseases, because it exerts synergetic actions on muscle fibers and vessels, which could enforce oxidative metabolism and ameliorate muscle performance.

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Related in: MedlinePlus

Variations in gene expression in EDL muscle induced by hindlimb-unloading and spaceflight.Transcript levels were determined by real-time PCR for selected genes, classified on the basis of the functional role of the protein they encode, and normalized for the housekeeping HPRT-1 gene. The bars indicate the fold change in gene expression between A) HU and ground conditions in WT mice, B) PTN and WT mice in ground conditions, C) PTN-HU versus WT-G mice, and D) spaceflown PTN mice versus ground WT mice. Significant fold changes, according to two-tailed unpaired Student’s t-test, are indicated with* (at least P<0.05).
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pone-0072028-g008: Variations in gene expression in EDL muscle induced by hindlimb-unloading and spaceflight.Transcript levels were determined by real-time PCR for selected genes, classified on the basis of the functional role of the protein they encode, and normalized for the housekeeping HPRT-1 gene. The bars indicate the fold change in gene expression between A) HU and ground conditions in WT mice, B) PTN and WT mice in ground conditions, C) PTN-HU versus WT-G mice, and D) spaceflown PTN mice versus ground WT mice. Significant fold changes, according to two-tailed unpaired Student’s t-test, are indicated with* (at least P<0.05).

Mentions: We evaluated the adaptation changes of gene expression due to PTN overexpression in ground and actual and simulated microgravity by measuring the shifts in mRNA levels of selected genes, including genes involved in muscle atrophy and metabolism, genes encoding sarcolemma ion channels, and genes involved in angiogenesis. To investigate the effects of HU in WT mice and effects of PTN in all experimental conditions (ground, HU, and SF), we report the gene expression level ratio in Sol (Fig. 7) and EDL (Fig. 8) muscles as a comparison between A) HU and ground conditions in WT mice, B) PTN and WT mice in ground conditions, C) PTN-HU versus WT-G mice, and D) PTN-SF mice versus ground WT mice. Effects of SF on selected gene expression in Sol and EDL muscles of WT mice have been previously reported [13].


Effects of pleiotrophin overexpression on mouse skeletal muscles in normal loading and in actual and simulated microgravity.

Camerino GM, Pierno S, Liantonio A, De Bellis M, Cannone M, Sblendorio V, Conte E, Mele A, Tricarico D, Tavella S, Ruggiu A, Cancedda R, Ohira Y, Danieli-Betto D, Ciciliot S, Germinario E, Sandonà D, Betto R, Camerino DC, Desaphy JF - PLoS ONE (2013)

Variations in gene expression in EDL muscle induced by hindlimb-unloading and spaceflight.Transcript levels were determined by real-time PCR for selected genes, classified on the basis of the functional role of the protein they encode, and normalized for the housekeeping HPRT-1 gene. The bars indicate the fold change in gene expression between A) HU and ground conditions in WT mice, B) PTN and WT mice in ground conditions, C) PTN-HU versus WT-G mice, and D) spaceflown PTN mice versus ground WT mice. Significant fold changes, according to two-tailed unpaired Student’s t-test, are indicated with* (at least P<0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756024&req=5

pone-0072028-g008: Variations in gene expression in EDL muscle induced by hindlimb-unloading and spaceflight.Transcript levels were determined by real-time PCR for selected genes, classified on the basis of the functional role of the protein they encode, and normalized for the housekeeping HPRT-1 gene. The bars indicate the fold change in gene expression between A) HU and ground conditions in WT mice, B) PTN and WT mice in ground conditions, C) PTN-HU versus WT-G mice, and D) spaceflown PTN mice versus ground WT mice. Significant fold changes, according to two-tailed unpaired Student’s t-test, are indicated with* (at least P<0.05).
Mentions: We evaluated the adaptation changes of gene expression due to PTN overexpression in ground and actual and simulated microgravity by measuring the shifts in mRNA levels of selected genes, including genes involved in muscle atrophy and metabolism, genes encoding sarcolemma ion channels, and genes involved in angiogenesis. To investigate the effects of HU in WT mice and effects of PTN in all experimental conditions (ground, HU, and SF), we report the gene expression level ratio in Sol (Fig. 7) and EDL (Fig. 8) muscles as a comparison between A) HU and ground conditions in WT mice, B) PTN and WT mice in ground conditions, C) PTN-HU versus WT-G mice, and D) PTN-SF mice versus ground WT mice. Effects of SF on selected gene expression in Sol and EDL muscles of WT mice have been previously reported [13].

Bottom Line: PTN overexpression did not prevent soleus muscle atrophy, slow-to-fast transition, and capillary regression induced by SF and HU.The numerous effects of PTN on muscle gene expression and functional parameters demonstrate the sensitivity of muscle fibers to the cytokine.Although little benefit was found in HU muscle disuse, PTN may emerge useful in various muscle diseases, because it exerts synergetic actions on muscle fibers and vessels, which could enforce oxidative metabolism and ameliorate muscle performance.

View Article: PubMed Central - PubMed

Affiliation: Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari, Italy.

ABSTRACT
Pleiotrophin (PTN) is a widespread cytokine involved in bone formation, neurite outgrowth, and angiogenesis. In skeletal muscle, PTN is upregulated during myogenesis, post-synaptic induction, and regeneration after crushing, but little is known regarding its effects on muscle function. Here, we describe the effects of PTN on the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles in mice over-expressing PTN under the control of a bone promoter. The mice were maintained in normal loading or disuse condition, induced by hindlimb unloading (HU) for 14 days. Effects of exposition to near-zero gravity during a 3-months spaceflight (SF) into the Mice Drawer System are also reported. In normal loading, PTN overexpression had no effect on muscle fiber cross-sectional area, but shifted soleus muscle toward a slower phenotype, as shown by an increased number of oxidative type 1 fibers, and increased gene expression of cytochrome c oxidase subunit IV and citrate synthase. The cytokine increased soleus and EDL capillary-to-fiber ratio. PTN overexpression did not prevent soleus muscle atrophy, slow-to-fast transition, and capillary regression induced by SF and HU. Nevertheless, PTN exerted various effects on sarcolemma ion channel expression/function and resting cytosolic Ca(2+) concentration in soleus and EDL muscles, in normal loading and after HU. In conclusion, the results show very similar effects of HU and SF on mouse soleus muscle, including activation of specific gene programs. The EDL muscle is able to counterbalance this latter, probably by activating compensatory mechanisms. The numerous effects of PTN on muscle gene expression and functional parameters demonstrate the sensitivity of muscle fibers to the cytokine. Although little benefit was found in HU muscle disuse, PTN may emerge useful in various muscle diseases, because it exerts synergetic actions on muscle fibers and vessels, which could enforce oxidative metabolism and ameliorate muscle performance.

Show MeSH
Related in: MedlinePlus