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.

The role of pleiotrophin in bone repair

“…The second category included the studies, which examined actions and possible mechanisms of PTN [8,[21][22][23][24][25][26][27] or its receptors [8,16,17,[28][29][30][31] actions in bone cells. The third category comprised of the studies, which investigate the macroscopic effects of altered PTN expression on bone formation and/or remodelling in animal models [8,[32][33][34][35][36][37][38][39][40] or in clinical studies [41]. Finally, the fourth category included articles on the regulation of PTN expression in cells of the skeletal system and/or by factors known to play a role in bone repair or remodelling [42][43][44][45][46][47][48][49][50][51][52][53][54], as well as data on the PTN actions related to angiogenesis .…”

“…PTN over-expressing mice exposed to normal gravity present a poorer trabecular organization than wild type mice but the expression of PTN during the flight offers some protection against microgravity's negative effects, as a result of a higher osteoblast activity in the flight mice [38]. A subsequent study showed that the reduction in the expression of collagen type I and osteocalcin in PTN transgenic mice was less than in the samples from wild type mice, possibly due to the higher level calcitonin expression that could participate to the protective effect of PTN over-expression on the bone damage [39].…”

Central Depletion of Brain-Derived Neurotrophic Factor in Mice Results in High Bone Mass and Metabolic Phenotype

“…To obtain RNA from bone, the femur and humerus bones were mechanically disrupted in TriReagent using a homogenizer (UltraTurraxH; IKAH-Werke GmbH and Co., Staufen, Germany) as described (32). Total RNA used for BDNF expression was treated with deoxyribonuclease I (Ambion, Austin, TX) to remove any DNA contamination because the primers/probes used for BDNF expression target a coding region with no introns.…”

Effects of microgravity simulation on zebrafish transcriptomes and bone physiology—exposure starting at 5 days post fertilization

“…29 Microgravity caused effects ranging from decreased trabecular numbers 27,29 and thickness 27 in tibia to a decreased mineral content and number of osteoblasts. 26,28,30 In astronauts, bone formation markers (type I procollagen propeptide and bone alkaline phosphatase) decreased, while bone resorption markers such as the procollagen C-telopeptide increased during space flight.…”