D-Mannose prevents bone loss under weightlessness

Ranli Gu; Hao Liu; Menglong Hu; Yuan Zhu; Xuenan Liu; Feilong Wang; Likun Wu; Danyang Song; Yunsong Liu

doi:10.1186/s12967-022-03870-1

D-Mannose prevents bone loss under weightlessness

J Transl Med. 2023 Jan 9;21(1):8. doi: 10.1186/s12967-022-03870-1.

Authors

Ranli Gu¹, Hao Liu², Menglong Hu¹, Yuan Zhu¹, Xuenan Liu¹, Feilong Wang¹, Likun Wu¹, Danyang Song¹, Yunsong Liu³

Affiliations

¹ Department of Prosthodontics, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
² The Central Laboratory, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
³ Department of Prosthodontics, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China. kqliuyunsong@hsc.pku.edu.cn.

Abstract

Background: Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness.

Methods: The hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection.

Results: The TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 [NFATc1]). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose.

Conclusion: D-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.

Keywords: Bone; Cell fusion; D-mannose; Osteoclast; UTI; Weightlessness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Density
Bone Diseases, Metabolic*
Bone Resorption* / metabolism
Bone Resorption* / prevention & control
Humans
Mannose / metabolism
Mannose / pharmacology
Osteoclasts
Rats
Weightlessness* / adverse effects
X-Ray Microtomography

Substances

Mannose