An Inulin-Type Atractylodes Macrocephala Polysaccharide Alleviates Weightlessness-Induced Bone Loss in Association with the Nrf2/HO-1 Pathway.

Background

Prolonged exposure to microgravity during spaceflight leads to significant bone loss. The phenomenon of weightlessness-induced bone loss (WIBL) continues to intensify as the flight time increases and this has attracted considerable attention of scholars.

Methods

In this study, proteomic analysis was performed to identify potential signaling pathways involved in WIBL. Subsequently, the effectiveness of Atractylodes macrocephala polysaccharide (AMP) 1-1 on WIBL was investigated using a rat hindlimb suspension (HLS) model and a co-culture model of osteoblasts and RAW264.7 cell line.

Results

It was found that AMP1-1 treatment improved bone microarchitecture, reduced the bone transformation rate, and enhanced bone biomechanical properties in the HLS model. In the cell co-culture system, AMP1-1 significantly inhibited osteoclastic differentiation, promoted osteoblastic differentiation, and attenuated osteoblastic apoptosis. The interaction between the nuclear factor erythroid 2-related factor 2 (Nrf2) system and antioxidant enzymes represented a key pathway mediating WIBL. Further investigation confirmed that AMP1-1 facilitated the nuclear translocation of Nrf2, up-regulated heme oxygenase-1 protein expression, and enhanced the transcription of downstream antioxidant enzymes. Consequently, it maintained bone homeostasis and protected against bone loss.

Conclusions

Our findings demonstrate that AMP1-1 protects against WIBL by modulating the Nrf2 pathway and suppressing oxidative stress, offering a potential therapeutic strategy for mitigating bone loss in weightless environments.