PLGA/BGP/Nef Porous Composite Restrains Osteoclasts by Inhibiting the NF-κB Pathway, Enhances IGF-1-mediated Osteogenic Differentiation and Promotes Bone Regeneration

Overview

Journal J Biol Eng

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2023 Jul 17

PMID 37461106

Authors

Feng Wu

Zhenxu Wu

Zhijun Ye

Guoqing Niu

Zhiliang Ma

Peibiao Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Novel bone substitutes are urgently needed in experimental research and clinical orthopaedic applications. There are many traditional Chinese medicines that have effects on bone repair. However, application of natural medicines in traditional Chinese medicine to bone tissue engineering and its mechanism were rarely reported.

Results: In this study, the osteogenic ability of bioactive glass particles (BGPs) and the osteogenic and osteoclastic ability of neferine (Nef) were fused into PLGA-based bone tissue engineering materials for bone regeneration. BGPs were prepared by spray drying and calcination. Particles and Nef were then mixed with PLGA solution to prepare porous composites by the phase conversion method. Here we showed that Nef inhibited proliferation and enhanced ALP activity of MC3T3-E1 cells in a dose- and time-dependent manner. And the composites containing Nef could also inhibit RANKL-induced osteoclast formation (p < 0.05). Mechanistically, the PLGA/BGP/Nef composite downregulated the expression of NFATC1 by inhibiting the NF-κB pathway to restrain osteoclasts. In the other hands, PLGA/BGP/Nef composite was first demonstrated to effectively activate the IGF-1R/PI3K/AKT/mTOR pathway to enhance IGF-1-mediated osteogenic differentiation. The results of animal experiments show that the material can effectively promote the formation and maturation of new bone in the skull defect site.

Conclusions: The PLGA/BGP/Nef porous composite can restrain osteoclasts by inhibiting the NF-κB pathway, enhance IGF-1-mediated osteogenic differentiation and promotes bone regeneration, and has the potential for clinical application.

Citing Articles

Signaling Pathways Driving MSC Osteogenesis: Mechanisms, Regulation, and Translational Applications.

Wang L, Ruan M, Bu Q, Zhao C Int J Mol Sci. 2025; 26(3).

PMID: 39941080 PMC: 11818554. DOI: 10.3390/ijms26031311.

References

Elgali I, Igawa K, Palmquist A, Lenneras M, Xia W, Choi S . Molecular and structural patterns of bone regeneration in surgically created defects containing bone substitutes. Biomaterials. 2014; 35(10):3229-42. DOI: 10.1016/j.biomaterials.2013.12.084. View

Peng Z, Xu R, You Q . Role of Traditional Chinese Medicine in Bone Regeneration and Osteoporosis. Front Bioeng Biotechnol. 2022; 10:911326. PMC: 9194098. DOI: 10.3389/fbioe.2022.911326. View

Chen S, Chu B, Chen Y, Cheng X, Guo D, Chen L . Neferine suppresses osteoclast differentiation through suppressing NF-κB signal pathway but not MAPKs and promote osteogenesis. J Cell Physiol. 2019; 234(12):22960-22971. DOI: 10.1002/jcp.28857. View

Chen J, Long F . mTOR signaling in skeletal development and disease. Bone Res. 2018; 6:1. PMC: 5802487. DOI: 10.1038/s41413-017-0004-5. View

Zhou Y, Wu Y, Ma W, Jiang X, Takemra A, Uemura M . The effect of quercetin delivery system on osteogenesis and angiogenesis under osteoporotic conditions. J Mater Chem B. 2020; 5(3):612-625. DOI: 10.1039/c6tb02312f. View

Marthandam Asokan S, Mariappan R, Muthusamy S, Velmurugan B . Pharmacological benefits of neferine - A comprehensive review. Life Sci. 2018; 199:60-70. DOI: 10.1016/j.lfs.2018.02.032. View

Liu X, Ma Y, Chen M, Ji J, Zhu Y, Zhu Q . Ba/Mg co-doped hydroxyapatite/PLGA composites enhance X-ray imaging and bone defect regeneration. J Mater Chem B. 2021; 9(33):6691-6702. DOI: 10.1039/d1tb01080h. View

Omar O, Dahlin A, Gasser A, Dahlin C . Tissue dynamics and regenerative outcome in two resorbable non-cross-linked collagen membranes for guided bone regeneration: A preclinical molecular and histological study in vivo. Clin Oral Implants Res. 2017; 29(1):7-19. DOI: 10.1111/clr.13032. View

Ogay V, Mun E, Kudaibergen G, Baidarbekov M, Kassymbek K, Zharkinbekov Z . Progress and Prospects of Polymer-Based Drug Delivery Systems for Bone Tissue Regeneration. Polymers (Basel). 2020; 12(12). PMC: 7760650. DOI: 10.3390/polym12122881. View

10.

Greenfield E, Bi Y, Miyauchi A . Regulation of osteoclast activity. Life Sci. 1999; 65(11):1087-102. DOI: 10.1016/s0024-3205(99)00156-3. View

11.

Walia B, Lingenheld E, Duong L, Sanjay A, Drissi H . A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair. Ann N Y Acad Sci. 2018; 1415(1):57-68. DOI: 10.1111/nyas.13629. View

12.

Wang Z, Chen L, Wang Y, Chen X, Zhang P . Improved Cell Adhesion and Osteogenesis of op-HA/PLGA Composite by Poly(dopamine)-Assisted Immobilization of Collagen Mimetic Peptide and Osteogenic Growth Peptide. ACS Appl Mater Interfaces. 2016; 8(40):26559-26569. DOI: 10.1021/acsami.6b08733. View

13.

Komori T . Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2. Int J Mol Sci. 2019; 20(7). PMC: 6480215. DOI: 10.3390/ijms20071694. View

14.

Song I, Kim J, Kim K, Jin H, Youn B, Kim N . Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation. FEBS Lett. 2009; 583(14):2435-40. DOI: 10.1016/j.febslet.2009.06.047. View

15.

Ritter N, Farach-Carson M, Butler W . Evidence for the formation of a complex between osteopontin and osteocalcin. J Bone Miner Res. 1992; 7(8):877-85. DOI: 10.1002/jbmr.5650070804. View

16.

Liu H, Li X, Lin J, Lin M . Morroniside promotes the osteogenesis by activating PI3K/Akt/mTOR signaling. Biosci Biotechnol Biochem. 2021; 85(2):332-339. DOI: 10.1093/bbb/zbaa010. View

17.

Zhou M, Guo M, Shi X, Ma J, Wang S, Wu S . Synergistically Promoting Bone Regeneration by Icariin-Incorporated Porous Microcarriers and Decellularized Extracellular Matrix Derived From Bone Marrow Mesenchymal Stem Cells. Front Bioeng Biotechnol. 2022; 10:824025. PMC: 9021399. DOI: 10.3389/fbioe.2022.824025. View

18.

Huang Z, Wan Y, Zhu X, Zhang P, Yang Z, Yao F . Simultaneous engineering of nanofillers and patterned surface macropores of graphene/hydroxyapatite/polyetheretherketone ternary composites for potential bone implants. Mater Sci Eng C Mater Biol Appl. 2021; 123:111967. DOI: 10.1016/j.msec.2021.111967. View

19.

Bharathi Priya L, Huang C, Hu R, Balasubramanian B, Baskaran R . An updated review on pharmacological properties of neferine-A bisbenzylisoquinoline alkaloid from Nelumbo nucifera. J Food Biochem. 2021; 45(12):e13986. DOI: 10.1111/jfbc.13986. View

20.

Al-Harbi N, Mohammed H, Al-Hadeethi Y, Bakry A, Umar A, Hussein M . Silica-Based Bioactive Glasses and Their Applications in Hard Tissue Regeneration: A Review. Pharmaceuticals (Basel). 2021; 14(2). PMC: 7909272. DOI: 10.3390/ph14020075. View