Bafilomycin A1 mitigates subchondral bone degeneration and pain in TMJOA rats.

BACKGROUND

Pain and disability are primary concerns for temporomandibular joint osteoarthritis (TMJOA) patients, and the efficacy of current treatments remains controversial. Overactive osteoclasts are associated with subchondral bone degeneration and pain in OA. The vacuolar H+-ATPase (V-ATPase) is crucial for differentiation and function in osteoclasts, but its role in TMJOA is not well defined. This study aims to evaluate the effects of the V-ATPase inhibitor, bafilomycin A1 (Baf A1) on the progression and pain of TMJOA.

MATERIALS AND

METHODS

Pain behavior tests, histological staining, tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining, and micro-CT analysis were conducted to evaluate the therapeutic efficacy of Baf A1 in monosodium iodoacetate-induced TMJOA in rats. Additionally, TRAP staining, enzyme-linked immunosorbent assay and immunofluorescence staining were used to assess the inhibitory effects of Baf a1 on the osteoclastogenesis, secretion of netrin-1 and neurite growth of trigeminal ganglion (TG) neurons.

RESULTS

Baf A1 significantly mitigated subchondral bone degeneration by suppressing osteoclastogenesis and subsequently inhibited cartilage degradation in TMJOA rats. Baf A1 also effectively alleviated pain behavior by inhibiting expression of netrin-1 and innervation of sensory nerve in TMJOA rats. In vitro assays of osteoclast and TG further demonstrated the inhibitory effects of Baf A1 on osteoclastogenesis, secretion of netrin-1 and neurite outgrowth of TG.

CONCLUSIONS

This study demonstrates that Baf A1 inhibits V-ATPase to mitigate TMJOA degeneration and pain by suppressing osteoclastogenesis and secretion of netrin-1, thereby suggesting it as a potential clinical treatment option for degeneration and pain of TMJOA.