Abstract
Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. The Nanoparticles and Osteoporosis (NATO) project aimed to develop innovative countermeasures for secondary osteoporosis affecting astronauts after prolonged periods in space microgravity. Calcium- and Strontium-containing hydroxyapatite nanoparticles (nCa-HAP and nSr-HAP, respectively) were previously developed and chemically characterized. This study constitutes the first investigation of the effect of the exogenous addition of nCa-HAP and nSr-HAP on bone remodeling in gravity (1 g), Random Positioning Machine (RPM) and onboard International Space Station (ISS) using human bone marrow mesenchymal stem cells (hBMMSCs). In 1 g conditions, nSr-HAP accelerated and improved the commitment of cells to differentiate towards osteoblasts, as shown by the augmented alkaline phosphatase (ALP) activity and the up-regulation of the expression of bone marker genes, supporting the increased extracellular bone matrix deposition and mineralization. The nSr-HAP treatment exerted a protective effect on the microgravity-induced reduction of ALP activity in RPM samples, and a promoting effect on the deposition of hydroxyapatite crystals in either ISS or 1 g samples. The results indicate the exogenous addition of nSr-HAP could be potentially used to deliver Sr to bone tissue and promote its regeneration, as component of bone substitute synthetic materials and additive for pharmaceutical preparation or food supplementary for systemic distribution.
Highlights
Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications
This paper, as indicated above, is the first report of our work on the effect exerted by the exogenous addition of nCa-HAP and nSr-HAP suspensions on hBM-MSCs in 3 different conditions: on the ground at 1 g, in the Random Positioning Machine (RPM) and in space, onboard the International Space Station (ISS)
Since the in vitro stem cells differentiation into osteoblasts is completed in approximately 28 days in the presence of an osteogenic medium (OM), we evaluated the effect of the addition of both types of nanoparticles to hBM-MSCs cultured for 28 days in proliferative medium (PM, without osteogenic factors) in 1 g conditions
Summary
Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. Imbalance in the regulation of these processes may result in osteoporosis, a systemic skeletal condition that is characterized by low bone mass, reduced bone strength and loss of the bone microarchitecture/mineralization These conditions affect the mechanical properties of bone tissue, leading to an increased risk of fracture due to the decreased density and increased bone fragility[1]. In vitro and in vivo studies have established that Sr (administered as Sr chloride, ranelate and lactate) increases bone formation and reduces bone resorption, leading to a gain in bone mass and the improvement of bone mechanical properties in healthy animals and humans[6,7]. It is the case, that these osteoporotic drugs, mainly Sr ranelate, may present contraindications with long-term use due to bioavailability or toxicity issues it has been argued that these could be limited by following precise recommendations[8]
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