Nutraceuticals Synergistically Promote Osteogenesis in Cultured 7F2 Osteoblasts and Mitigate Inhibition of Differentiation and Maturation in Simulated Microgravity

Abstract

Microgravity is known to impact bone health, similar to mechanical unloading on Earth. In the absence of countermeasures, bone formation and mineral deposition are strongly inhibited in Space. There is an unmet need to identify nutritional countermeasures. Curcumin and carnosic acid are phytonutrients with anticancer, anti-inflammatory, and antioxidative effects and may exhibit osteogenic properties. Zinc is a trace element essential for bone formation. We hypothesized that these nutraceuticals could counteract the microgravity-induced inhibition of osteogenic differentiation and function. To test this hypothesis, we cultured 7F2 murine osteoblasts in simulated microgravity (SMG) in a Random Positioning Machine in the presence and absence of curcumin, carnosic acid, and zinc and evaluated cell proliferation, function, and differentiation. SMG enhanced cell proliferation in osteogenic medium. The nutraceuticals partially reversed the inhibitory effects of SMG on alkaline phosphatase (ALP) activity and did not alter the SMG-induced reduction in the expression of osteogenic marker genes in osteogenic medium, while they promoted osteoblast proliferation and ALP activity in the absence of traditional osteogenic media. We further observed a synergistic effect of the intermix of the phytonutrients on ALP activity. Intermixes of phytonutrients may serve as convenient and effective nutritional countermeasures against bone loss in space.

Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review

“…Antioxidants (AO) only showed a positive effect on BL in animal and cell studies [ 72 , 75 ], but not in human studies [ 63 ].…”

“…Application of AO had an effect in studies on cells and animals. Both nutraceuticals and polyphenols have an elevating effect on ALP activity in OBs exposed to s-µ g [ 72 , 75 ]. The reduced BL in rats could be due to alleviation of the µ g -induced inhibition of Wnt/β-catenin pathway, which enhances BF, because ALP, N-terminal propeptide of type 1 procollagen, and β-catenin are increased [ 72 ].…”

Moringa oleifera leaf extract induces osteogenic-like differentiation of human osteosarcoma SaOS2 cells

“…A previous study has reported that nutraceuticals curcumin and carnosic acid synergistically promoted osteogenesis in cultured murine 7F2 osteoblast cells and alleviated microgravity-induced inhibition of osteogenic differentiation and function. 41 …”

Paradoxical role of reactive oxygen species in bone remodelling: implications in osteoporosis and possible nanotherapeutic interventions

“…Increased levels of ROS may further block the osteoblast activities and their differentiation followed by low intensity of mineralization and minimal osteogenesis [55,56]. However, antioxidants have a paradoxical effect, as they help in differentiation of osteoblasts followed by formation of bone [31,[57][58][59], maintain osteocytes required for osteogenesis, while simultaneously they minimise the osteoclast activities and their differentiation. Osteoclast and osteoblast activities are regulated by various factors which are produced by osteoblasts themselves and also by osteocytes for the bone remodelling such as receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG).…”

“…These antioxidants are not only direct scavengers of ROS but also maintain significant levels of GSH for the conjugation with GSH reductase. Thus, they can eliminate GSSG and can sustain the standard GSH/GSSG levels thereby balancing the intracellular redox state [32,57,59]. Consequences of antioxidants on bone metabolism have been reported, suggesting the low levels of antioxidants presented in plasma of aged or osteoporotic animals [77].…”