Selcopintide (SCPT) restores cellular homeostasis and Nrf2 activity, significantly attenuating alveolar bone loss in periodontitis.

Periodontitis is a debilitating chronic inflammatory disease marked by persistent inflammation, redox imbalance, and mitochondrial dysfunction, leading to impaired cellular function and tissue integrity. Current therapies primarily manage inflammation and promote regeneration, but often fail to restore the fundamental function of resident cells compromised by the inflammatory microenvironment. This gap highlights the need for strategies that re-establish cellular homeostasis before or during regeneration to enhance treatment outcomes. This study investigates CPNE7's role in periodontal homeostasis and evaluates its derived peptide, selcopintide (SCPT), as a therapeutic agent.

Researchers investigated CPNE7's role in periodontal homeostasis and tested selcopintide (SCPT), a CPNE7-derived peptide, in both in vitro inflammatory conditions and a mouse ligature-induced periodontitis model. They assessed CPNE7 expression in aged periodontal tissues and induced periodontitis in Cpne7 knockout mice to observe structural abnormalities and inflammatory responses. For therapeutic evaluation, SCPT was administered topically to mice with ligature-induced periodontitis. Key endpoints included reactive oxygen species (ROS) accumulation, redox balance, mitochondrial function (morphology, bioenergetics), inflammatory signaling, apoptosis, and alveolar bone loss, using assays like qPCR and histological analysis.

CPNE7 expression was significantly reduced in aged periodontal tissues, accompanied by increased oxidative stress and decreased Nrf2 expression. Cpne7 knockout mice exhibited periodontal structural abnormalities and showed aggravated alveolar bone loss and inflammatory responses following periodontitis induction. In vitro, SCPT reduced excessive reactive oxygen species (ROS) accumulation induced by inflammatory stimuli and restored redox balance, thereby supporting cellular homeostasis. Furthermore, SCPT improved mitochondrial function under inflammatory conditions, evidenced by restored mitochondrial morphology and bioenergetic function, while attenuating inflammatory signaling and apoptosis. These protective effects were consistently associated with the activation of the Nrf2 antioxidant pathway. Importantly, in the in vivo model:

Topical administration of SCPT significantly attenuated periodontal destruction and alveolar bone loss in the ligature-induced periodontitis model, demonstrating its therapeutic efficacy.