Smart Nanosacrificial Layer on the Bone Surface Prevents Osteoporosis through Acid-Base Neutralization Regulated Biocascade Effects.

Abstract

Osteoporosis is a global chronic disease characterized by severe bone loss and high susceptibility to fragile fracture. It is widely accepted that the origin acidified microenvironment created by excessive osteoclasts causes irreversible bone mineral dissolution and organic degradation during osteoclastic resorption. However, current clinically available approaches are mainly developed from the perspective of osteoclast biology rather than the critical acidified niche. Here, we developed a smart "nanosacrificial layer" consisting of sodium bicarbonate (NaHCO3)-containing and tetracycline-functionalized nanoliposomes (NaHCO3-TNLs) that can target bone surfaces and respond to external secreted acidification from osteoclasts, preventing osteoporosis. In vitro and in vivo results prove that this nanosacrificial layer precisely inhibits the initial acidification of osteoclasts and initiates a chemically regulated biocascade to remodel the bone microenvironment and realize bone protection: extracellular acid-base neutralization first inhibits osteoclast function and also promotes its apoptosis, in which the apoptosis-derived extracellular vesicles containing RANK (receptor activator of nuclear factor-κ B) further consume RANKL (RANK ligand) in serum, achieving comprehensive osteoclast inhibition. Our therapeutic strategy for osteoporosis is based on original and precise acid-base neutralization, aiming to reestablish bone homeostasis by using a smart nanosacrificial layer that is able to induce chemically regulated biocascade effects. This study also provides a novel understanding of osteoporosis therapy in biomedicine and clinical treatments.

• Authors: Xianfeng Lin, Qingqing Wang, Chenhui Gu, Mobai Li, Kai Chen, Pengfei Chen, Zhibin Tang, Xin Liu, Haihua Pan, Zhaoming Liu, Ruikang Tang, Shunwu Fan
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 142 Issue 41 Pg. 17543-17556 (10 14 2020) ISSN: 1520-5126 [Electronic] United States
• PMID: 32960592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,2-dioleoyl-3-phosphoethanolamine-n-(poly(ethyleneglycol))-hydroxy succinamide
• Lecithins
• NF-kappa B
• Phosphatidylethanolamines
• RANK Ligand
• Carbon Dioxide
• Polyethylene Glycols
• Sodium Bicarbonate
• Cholesterol
• Tetracycline

Topics

• Animals
• Bone Resorption (metabolism)
• Bone and Bones (metabolism)
• Carbon Dioxide (chemistry)
• Cholesterol (chemistry)
• Female
• Humans
• Lecithins (chemistry)
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Nanostructures (chemistry)
• Osteoclasts (metabolism)
• Osteoporosis (prevention & control)
• Phosphatidylethanolamines (chemistry, metabolism)
• Polyethylene Glycols (chemistry, metabolism)
• RANK Ligand (metabolism)
• Sodium Bicarbonate (chemistry)
• Surface Properties
• Tetracycline (chemistry)