Role of the NF-kB signalling pathway in heterotopic ossification: biological and therapeutic significance.
Cell Commun Signal
; 22(1): 159, 2024 03 04.
Article
em En
| MEDLINE
| ID: mdl-38439078
ABSTRACT
Heterotopic ossification (HO) is a pathological process in which ectopic bone develops in soft tissues within the skeletal system. Endochondral ossification can be divided into the following types of acquired and inherited ossification traumatic HO (tHO) and fibrodysplasia ossificans progressiva (FOP). Nuclear transcription factor kappa B (NF-κB) signalling is essential during HO. NF-κB signalling can drive initial inflammation through interactions with the NOD-like receptor protein 3 (NLRP3) inflammasome, Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK). In the chondrogenesis stage, NF-κB signalling can promote chondrogenesis through interactions with mechanistic target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/AKT (protein kinase B, PKB) and other molecules, including R-spondin 2 (Rspo2) and SRY-box 9 (Sox9). NF-κB expression can modulate osteoblast differentiation by upregulating secreted protein acidic and rich in cysteine (SPARC) and interacting with mTOR signalling, bone morphogenetic protein (BMP) signalling or integrin-mediated signalling under stretch stimulation in the final osteogenic stage. In FOP, mutated ACVR1-induced NF-κB signalling exacerbates inflammation in macrophages and can promote chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs) through interactions with smad signalling and mTOR signalling. This review summarizes the molecular mechanism of NF-κB signalling during HO and highlights potential therapeutics for treating HO.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Ossificação Heterotópica
Limite:
Humans
Idioma:
En
Revista:
Cell Commun Signal
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China