Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Berberine facilitates alveolar bone regeneration via Ptgs2-mediated dual regulation of osteoblast differentiation and fibroblast inhibition.
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Li Tian, Lin Shanfeng, Cao Hongjuan, Hasi Dalai, Liu Xiaohan, Wu Lin
Аннотация
BACKGROUND: Guided bone regeneration (GBR) is widely used for localized bone augmentation in the oral-maxillofacial region, but traditional GBR membranes are limited by their biofunctionality and mechanical properties. Berberine (BBR) has been reported to inhibit fibrosis and promote bone regeneration, yet it remains unclear whether BBR can simultaneously suppress fibroblast activity while enhancing osteogenic differentiation.
PURPOSE: This study aims to identify the optimal BBR concentration and its dual mechanisms in inhibiting fibroblast proliferation while promoting osteogenic differentiation, potentially providing an alternative to the barrier function of traditional GBR membranes.
METHODS: The optimal BBR concentration and its effects on fibroblast proliferation and osteogenic differentiation were evaluated in vitro. Network pharmacology and proteomics were used to investigate the potential mechanisms. A rat model of alveolar bone defects was used to evaluate the reparative effect of BBR. Seahorse analysis, electron microscopy, and immunofluorescence were employed to explore BBR's regulatory effect on mitochondrial function in both cell types.
RESULTS: BBR at 10 and 15 μM optimally promotes osteoblast dominance within the wound healing microenvironment, induces G1-phase arrest in fibroblasts, and promotes osteogenic differentiation. Mechanistically, BBR directly binds to prostaglandin-endoperoxide synthase 2 (Ptgs2) and upregulates Ptgs2 to achieve the dual effects. In vivo, the bone regeneration effect of the BBR and Bio-Oss® (a commercial bone substitute) combination was similar to that of the Bio-Oss® and Bio-Gide® combination (a commercial collagen membrane). Furthermore, distinct COX-2 localization patterns were observed following BBR treatment, with enhanced mitochondrial localization in osteoblasts and nuclear localization in fibroblasts, coupled with altered mitochondrial energy metabolism.
CONCLUSIONS: Our study suggests that optimal concentrations of BBR can inhibit fibroblast proliferation and promote osteogenic differentiation, thereby enhancing bone regeneration. Combined with spatial maintenance materials, BBR presents a promising alternative to traditional GBR membranes for improving clinical outcomes in oral bone augmentation and defect repair.
PURPOSE: This study aims to identify the optimal BBR concentration and its dual mechanisms in inhibiting fibroblast proliferation while promoting osteogenic differentiation, potentially providing an alternative to the barrier function of traditional GBR membranes.
METHODS: The optimal BBR concentration and its effects on fibroblast proliferation and osteogenic differentiation were evaluated in vitro. Network pharmacology and proteomics were used to investigate the potential mechanisms. A rat model of alveolar bone defects was used to evaluate the reparative effect of BBR. Seahorse analysis, electron microscopy, and immunofluorescence were employed to explore BBR's regulatory effect on mitochondrial function in both cell types.
RESULTS: BBR at 10 and 15 μM optimally promotes osteoblast dominance within the wound healing microenvironment, induces G1-phase arrest in fibroblasts, and promotes osteogenic differentiation. Mechanistically, BBR directly binds to prostaglandin-endoperoxide synthase 2 (Ptgs2) and upregulates Ptgs2 to achieve the dual effects. In vivo, the bone regeneration effect of the BBR and Bio-Oss® (a commercial bone substitute) combination was similar to that of the Bio-Oss® and Bio-Gide® combination (a commercial collagen membrane). Furthermore, distinct COX-2 localization patterns were observed following BBR treatment, with enhanced mitochondrial localization in osteoblasts and nuclear localization in fibroblasts, coupled with altered mitochondrial energy metabolism.
CONCLUSIONS: Our study suggests that optimal concentrations of BBR can inhibit fibroblast proliferation and promote osteogenic differentiation, thereby enhancing bone regeneration. Combined with spatial maintenance materials, BBR presents a promising alternative to traditional GBR membranes for improving clinical outcomes in oral bone augmentation and defect repair.