3'-Sialyllactose alleviates bone loss by regulating bone homeostasis.

Area of Science:

• Bone Biology and Metabolism
• Skeletal Diseases
• Pharmacology

Background:

• Osteoporosis is a prevalent skeletal disorder characterized by an elevated fracture risk, lacking definitive curative treatments.
• Human milk contains 3 '-Sialyllactose (3 '-SL), a bioactive oligosaccharide with diverse biological functions, but its role in bone metabolism is unexplored.

Purpose of the Study:

• To elucidate the molecular mechanisms by which 3 '-SL influences bone homeostasis.
• To evaluate the potential of 3 '-SL as a therapeutic agent for osteoporosis.

Main Methods:

• Human bone marrow stromal cells (hBMSCs) and bone marrow-derived macrophages were treated with 3 '-SL.
• Osteogenic and adipogenic differentiation assays were performed on hBMSCs.
• RNA sequencing was utilized to identify molecular changes.
• Osteoclast differentiation was assessed.
• An ovariectomized mouse model was employed to evaluate in vivo efficacy.

Main Results:

• 3 '-SL treatment enhanced osteogenic differentiation and suppressed adipogenic differentiation in hBMSCs.
• 3 '-SL upregulated laminin subunit gamma-2 expression, promoting osteogenesis via the PI3K/Akt pathway.
• 3 '-SL inhibited osteoclast differentiation through the NF-κB and MAPK pathways.
• In vivo studies demonstrated that 3 '-SL ameliorated osteoporosis in ovariectomized mice and positively regulated bone remodeling.

Conclusions:

• 3 '-SL modulates bone metabolism by promoting osteoblastogenesis and inhibiting osteoclastogenesis.
• The findings highlight 3 '-SL's potential as a novel therapeutic agent for managing osteoporosis.