title: Effects of pleiotrophin overexpression on mouse skeletal muscles in normal loading and in actual and simulated microgravity.
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.
authors.affiliation: Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari, Italy.
authors.forename: Giulia Maria
authors.initials: GM
authors.lastname: Camerino
authors.forename: Sabata
authors.initials: S
authors.lastname: Pierno
authors.forename: Antonella
authors.initials: A
authors.lastname: Liantonio
authors.forename: Michela
authors.initials: M
authors.lastname: De Bellis
authors.forename: Maria
authors.initials: M
authors.lastname: Cannone
authors.forename: Valeriana
authors.initials: V
authors.lastname: Sblendorio
authors.forename: Elena
authors.initials: E
authors.lastname: Conte
authors.forename: Antonietta
authors.initials: A
authors.lastname: Mele
authors.forename: Domenico
authors.initials: D
authors.lastname: Tricarico
authors.forename: Sara
authors.initials: S
authors.lastname: Tavella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ruggiu
authors.forename: Ranieri
authors.initials: R
authors.lastname: Cancedda
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
authors.forename: Daniela
authors.initials: D
authors.lastname: Danieli-Betto
authors.forename: Stefano
authors.initials: S
authors.lastname: Ciciliot
authors.forename: Elena
authors.initials: E
authors.lastname: Germinario
authors.forename: Dorianna
authors.initials: D
authors.lastname: Sandonà
authors.forename: Romeo
authors.initials: R
authors.lastname: Betto
authors.forename: Diana Conte
authors.initials: DC
authors.lastname: Camerino
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Desaphy
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D019417:Hindlimb Suspension; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D013026:Space Flight
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D007473:Ion Channels; D009124:Muscle Proteins; C066845:pleiotrophin; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D002118:Calcium