Loss Of Β-Arrestin2 Aggravated Cartilage Degeneration Of Early TMJOA

Temporomandibular joint osteoarthritis (TMJOA), characterized by cartilage degradation and inflammation, lacks early intervention targets. While β-arrestin2 modulates inflammatory pathways, its role in TMJOA initiation is unclear. This study investigates the mechanistic contributions of β-arrestin2 in early TMJOA pathogenesis. Unilateral anterior crossbite (UAC) models were used on eight-week-old wild-type (WT) and β-arrestin2 knockout (KO) mice to mimic early-stage TMJOA progression. Histomorphological alterations were evaluated through hematoxylin-eosin (HE) staining and micro-computed tomography (micro-CT). Immunohistochemical analyses quantified expression levels of degradative (Col-X), pro-inflammatory (TNF-α, IL-1β), and autophagy-related (BECN, LC3B-II) markers. Chondrocyte apoptosis was determined via TUNEL assay. β-arrestin2 KO mice exhibited aggravated TMJOA pathology after 3 weeks of UAC, with cartilage thickness reduced by 33% compared to WT-UAC controls. Micro-CT analysis revealed a 20% decrease in subchondral bone volume fraction (BV/TV) and a 22% greater trabecular separation (Tb.Sp) in KO-UAC mice. Cartilage degeneration was marked by a 1.4-fold increase in Col-X expression and 25%/47% elevation of TNF-α/IL-1β in KO-UAC specimens. Apoptotic chondrocytes (TUNEL+) increased by 105% in KO-UAC versus WT-UAC, accompanied by 1.52-fold higher LC3B-II accumulation, indicating autophagic dysregulation. Our findings establish β-arrestin2 as a novel protective mediator in early TMJOA pathogenesis, potentially through dual regulation of chondrocyte apoptosis and autophagy. These results propose β-arrestin2 modulation as a promising therapeutic strategy for arresting early TMJOA progression.