In the space microgravity environment, bone loss poses a formidable health challenge for astronauts. Dietary intake of renewable food components offers a feasible approach to mitigate bone loss associated with primary osteoporosis, aligning with the demands of long-term space missions. Recent research has highlighted the potential of Spirulina in ameliorating osteoporosis, with thermal processing enhancing the protein bioavailability. This study investigates the effects of different heat-treated Spirulina proteins (SPP) and their enzymatic hydrolysates on osteoporosis using a hindlimb suspension model (HLS) in mice to simulate microgravity conditions. The results demonstrate that heat-treated SPP and enzymatic hydrolysates significantly preserve skeletal morphology, suppress bone resorption, and enhance bone density, with the microwave-treated SPP hydrolysate (MWSPPH) showing the most pronounced improvement effects. Mechanistic insights reveal that MWSPPH enhances bone health by modulating the FoxO/Wnt/β-catenin signaling pathway. Specifically, MWSPPH reduces the expression of FoxO and facilitates the accumulation of β-catenin, while also indirectly modulating osteoclast-related signaling by altering RANKL and RANK expression. It also beneficially increases beneficial gut microbiota and the production of short-chain fatty acids, thereby improving bone density, suggesting its potential as a dietary strategy for managing osteoporosis in space environments.
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