title: Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS).
abstract: Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.
authors.affiliation: Dipartimento di Oncologia, Biologia e Genetica, Università degli Studi di Genova, Genova, Italy. sara.tavella@unige.it
authors.forename: Sara
authors.initials: S
authors.lastname: Tavella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ruggiu
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giuliani
authors.forename: Francesco
authors.initials: F
authors.lastname: Brun
authors.forename: Barbara
authors.initials: B
authors.lastname: Canciani
authors.forename: Adrian
authors.initials: A
authors.lastname: Manescu
authors.forename: Katia
authors.initials: K
authors.lastname: Marozzi
authors.forename: Michele
authors.initials: M
authors.lastname: Cilli
authors.forename: Delfina
authors.initials: D
authors.lastname: Costa
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Federica
authors.initials: F
authors.lastname: Piccardi
authors.forename: Roberta
authors.initials: R
authors.lastname: Tasso
authors.forename: Giuliana
authors.initials: G
authors.lastname: Tromba
authors.forename: Franco
authors.initials: F
authors.lastname: Rustichelli
authors.forename: Ranieri
authors.initials: R
authors.lastname: Cancedda
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000235:genetics* / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000000981:diagnostic imaging / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D016207:Cytokines / Q000235:genetics* / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010011:Osteocytes / Q000166:cytology / Q000502:physiology; D013026:Space Flight; D013141:Spiro Compounds; D016474:Weight-Bearing / Q000502:physiology; D014893:Weightlessness / Q000009:adverse effects*; D055114:X-Ray Microtomography
chemical_list: C529377:BAS 100; D002352:Carrier Proteins; D016207:Cytokines; D017931:DNA Primers; D013141:Spiro Compounds; C066845:pleiotrophin