Work

Puerarin‑Loaded pH‑Responsive ZIF‑90 Nanoparticles Ameliorate Osteoporosis via Enhancing H3K18 Lactylation and Suppressing Aberrant Osteoclast Activation

Year: 2026

Type: article

Abstract: Osteoporosis is characterized by dysregulated osteoclast activity, leading to excessive bone resorption and structural damage. In this study, we developed pH-responsive ZIF-90 nanoparticles loaded with puerarin (PU) (ZIF-90@PU) for microenvironment-responsive osteoporosis therapy through epigenetic modulation. Following self-assembly, the nanoparticles underwent dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS); these analyses verified efficient puerarin encapsulation and pH-triggered release. In cell-based experiments, ZIF-90@PU suppressed the differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts while promoting osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Administration of ZIF-90@PU to ovariectomized (OVX) mice produced significant gains in bone mineral density, trabecular architecture, and bone strength without detectable toxicity. Mechanistically, ZIF-90@PU treatment was associated with increased H3K18 lactylation and reduced NFATc1 signaling, accompanied by suppression of osteoclast activation. This study introduces ZIF-90@PU as a novel epigenetic-modulating nanomedicine for osteoporosis treatment.

Source: Advanced Science

DOI: 10.1002/advs.77869

Authors: Jiajia Lu, Yue Xi, Sheng Wang, Ye Chen, Jiajie Yang, Xiaojian Shi

Institution: Tongji University

Language: English

Topic: Bone Metabolism and Diseases

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,730