Porphyran Inhibits Osteoclast Formation Based on NF‐κB Signaling Pathways and Accelerates Alveolar Bone Healing in Ovariectomized Mice

ABSTRACT Osteoporosis is characterized by a disrupted bone remodeling process, with bone resorption exceeding bone formation, resulting in reduced bone mass and impaired bone defect healing. Porphyran (PYP), a sulfated polysaccharide extracted from seaweed, inhibits osteoclast differentiation in vitro. This study aimed to explore the effects of PYP on osteoblasts and osteoclasts and on bone defect healing in ovariectomized (OVX) mice. In vitro, osteogenic and osteoclastic differentiation was assessed in PYP‐treated MC3T3‐E1 and BMMs using ALP staining, Alizarin Red staining, TRAP staining, immunofluorescence, qPCR, and western blotting. In vivo, 8‐week‐old female C57BL/6 mice underwent ovariectomy followed by right maxillary incisor extraction to establish osteoporotic bone defects. The mice were divided into Sham, OVX, and PYP (OVX with PYP treatment) groups. The PYP group received daily oral gavage of PYP (200 mg/kg), while the Sham and OVX groups received equivalent saline volumes. Extraction socket healing progression was assessed at 0, 7, and 21 days post‐extraction using ELISA, qRT‐PCR, µCT scanning, and histomorphometric analysis. The results showed that PYP did not enhance osteoblast differentiation but inhibited osteoclast differentiation by suppressing the NF‐κB signaling pathway and promoted alveolar socket healing in OVX mice. In conclusion, porphyran promotes alveolar bone healing in osteoporotic mice by suppressing osteoclastogenesis via NF‐κB signaling inhibition, suggesting its therapeutic potential for bone metabolic disorders. Practical Applications Porphyran (PYP), a natural seaweed compound, shows promise for creating bone‐health supplements or dental recovery treatments. It helps reduce bone loss after procedures such as tooth extractions in osteoporosis patients while protecting the body's natural bone‐building process. This plant‐based solution could lead to safer clinical therapies for doctors and accessible natural products for people wanting stronger bones. Its gentle action makes it suitable for both medical use and everyday consumer health products.