Limits...
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.

Show MeSH

Related in: MedlinePlus

Muscle vascularization in wild-type and PTN-overexpressing mice after 14 days HU or 91 days space flight.A) Representative Sol muscle sections stained for alkaline phosphatase activity. Pictures of spaceflown samples (right column) were slightly modified using Photoshop software (Adobe) to increase contrast. B) The number of capillary was counted in Sol and EDL muscle sections stained as shown in A and normalized to the number of muscle fibers. Each bars is the mean capillary-to-fiber ratio ± SEM calculated from WT-ground (n = 6), WT-HU (n = 3), WT-spaceflown (n = 1), PTN-ground (n = 6), PTN-HU (n = 3), and PTN-spaceflown (n = 2) mice. Statistical analysis performed with two-tailed unpaired Student’s t test indicates significant change (P<0.05) versus WT-G (*) and PTN-G (#).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3756024&req=5

pone-0072028-g004: Muscle vascularization in wild-type and PTN-overexpressing mice after 14 days HU or 91 days space flight.A) Representative Sol muscle sections stained for alkaline phosphatase activity. Pictures of spaceflown samples (right column) were slightly modified using Photoshop software (Adobe) to increase contrast. B) The number of capillary was counted in Sol and EDL muscle sections stained as shown in A and normalized to the number of muscle fibers. Each bars is the mean capillary-to-fiber ratio ± SEM calculated from WT-ground (n = 6), WT-HU (n = 3), WT-spaceflown (n = 1), PTN-ground (n = 6), PTN-HU (n = 3), and PTN-spaceflown (n = 2) mice. Statistical analysis performed with two-tailed unpaired Student’s t test indicates significant change (P<0.05) versus WT-G (*) and PTN-G (#).

Mentions: It is noteworthy that muscle vascularization depends on muscle activity [20]. Muscle capillary regression has been observed in rats or mice after HU [21]–[24] and in rats after SF [25]. Thus we calculated the capillary-to-fiber (C/F) ratio in Sol and EDL muscle cryosections stained for alkaline phosphatase activity (Fig. 4A). As expected, HU significantly reduced the C/F ratio by 21% in atrophied Sol muscle, but had no effect on the EDL muscle of WT mice (Fig. 4B). The C/F ratio was also greatly reduced in the SF WT mouse. In ground conditions, the over-expression of PTN induced a significant increase of C/F ratio in both Sol (+17%) and EDL (+33%) muscles, suggesting pro-angiogenic effects of the trophic factor (Fig. 4B). Nevertheless, PTN over-expression was unable to prevent capillary regression in Sol muscle induced by either HU or SF.


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)

Muscle vascularization in wild-type and PTN-overexpressing mice after 14 days HU or 91 days space flight.A) Representative Sol muscle sections stained for alkaline phosphatase activity. Pictures of spaceflown samples (right column) were slightly modified using Photoshop software (Adobe) to increase contrast. B) The number of capillary was counted in Sol and EDL muscle sections stained as shown in A and normalized to the number of muscle fibers. Each bars is the mean capillary-to-fiber ratio ± SEM calculated from WT-ground (n = 6), WT-HU (n = 3), WT-spaceflown (n = 1), PTN-ground (n = 6), PTN-HU (n = 3), and PTN-spaceflown (n = 2) mice. Statistical analysis performed with two-tailed unpaired Student’s t test indicates significant change (P<0.05) versus WT-G (*) and PTN-G (#).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0072028-g004: Muscle vascularization in wild-type and PTN-overexpressing mice after 14 days HU or 91 days space flight.A) Representative Sol muscle sections stained for alkaline phosphatase activity. Pictures of spaceflown samples (right column) were slightly modified using Photoshop software (Adobe) to increase contrast. B) The number of capillary was counted in Sol and EDL muscle sections stained as shown in A and normalized to the number of muscle fibers. Each bars is the mean capillary-to-fiber ratio ± SEM calculated from WT-ground (n = 6), WT-HU (n = 3), WT-spaceflown (n = 1), PTN-ground (n = 6), PTN-HU (n = 3), and PTN-spaceflown (n = 2) mice. Statistical analysis performed with two-tailed unpaired Student’s t test indicates significant change (P<0.05) versus WT-G (*) and PTN-G (#).
Mentions: It is noteworthy that muscle vascularization depends on muscle activity [20]. Muscle capillary regression has been observed in rats or mice after HU [21]–[24] and in rats after SF [25]. Thus we calculated the capillary-to-fiber (C/F) ratio in Sol and EDL muscle cryosections stained for alkaline phosphatase activity (Fig. 4A). As expected, HU significantly reduced the C/F ratio by 21% in atrophied Sol muscle, but had no effect on the EDL muscle of WT mice (Fig. 4B). The C/F ratio was also greatly reduced in the SF WT mouse. In ground conditions, the over-expression of PTN induced a significant increase of C/F ratio in both Sol (+17%) and EDL (+33%) muscles, suggesting pro-angiogenic effects of the trophic factor (Fig. 4B). Nevertheless, PTN over-expression was unable to prevent capillary regression in Sol muscle induced by either HU or SF.

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