Stem cell therapy for intervertebral disc degeneration: Clinical progress with exosomes and gene vectors

Table 3 Comparison of signaling pathways and effects

Signaling pathway	Key factors	Regulatory mechanism	Functional effects
TGF-β signaling pathway	TGF-β, Smad2/3	Promotes ECM production and reduces cell apoptosis by activating the Smad pathway	Enhances the survival of NPCs, promotes type II collagen and proteoglycan production, maintains disc elasticity
Wnt/β-catenin pathway	β-catenin	Activates the translocation of β-catenin into the nucleus, regulating the expression of cartilage-related genes	Promotes differentiation of NPCs and chondrocyte-like cells, enhances ECM production, maintains disc structural integrity
PI3K/AKT pathway	PI3K, AKT, mTOR, Bcl-2	Enhances stem cell survival and reduces apoptosis of nucleus pulposus cells by activating mTOR and Bcl-2	Increases stem cell survival rate under hypoxic conditions, enhances regenerative ability, reduces inflammatory response
NF-κB signaling pathway	NF-κB, TNF-α, IL-6	Inhibits the expression of inflammation-related molecules like TNF-α, IL-6, and IL-1β associated with NF-κB, delays tissue damage, and reduces apoptosis of NPCs	Improves the survival rate of NPCs through anti-inflammatory and antiapoptotic effects, promoting tissue regeneration
Notch signaling pathway	Notch1, Notch2, CSL, NICD	Activates the CSL transcription factor through ligand binding, promoting stem cell proliferation and differentiation	Enhances the formation of NPCs and annulus fibrosus cells, increases the regenerative potential of disc tissue
HIF-1α signaling pathway	HIF-1α, IGF-1	Regulates the metabolism of NPCs and ECM synthesis, enhancing cell survival in a hypoxic microenvironment	Maintains disc tissue elasticity, reduces cell apoptosis, delays disc degeneration

TGF: Transforming growth factor; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; NF-κB: Nuclear factor-kappaB; mTOR: Mechanistic target of rapamycin; TNF: Tumor necrosis factor; IL: Interleukin; NICD: Notch intracellular domain; HIF: Hypoxia-inducible factor; IGF-1: Insulin-like growth factor 1; ECM: Extracellular matrix; NPC: Nucleus pulposus cells.