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In consideration of the lack of effective preventive or treatments options against infectious osteolysis, the exploitation of novel pharmacological compounds\/agents is critically required. The present study assessed the effect of protocatechualdehyde (PCA), a natural occurring polyphenolic compound with diverse biological activities including but not limited to antibacterial and antiinflammatory properties, on nuclear factor\u2010\u03baB ligand (RANKL)\u2010induced osteoclastogenesis in vitro and lipopolysaccharide (LPS)\u2010induced bone loss in vivo. In the present study, it was found that PCA potently inhibited RANKL\u2010induced osteoclast formation, fusion, and activation toward bone resorption in a dose\u2010dependent manner via the suppression of the ERK\/c\u2010Fos\/nuclear factor of activated T\u2010cells, cytoplasmic 1 signaling axis. It was further demonstrated that the in vivo administration of PCA could effectively protect mice against the deleterious effects of LPS\u2010induced calvarial bone destruction by attenuating osteoclast formation and activity in a dose\u2010dependent manner. Collectively, these findings provided evidence for the potential therapeutic application of PCA in the prevention and treatment of infectious osteolytic conditions, and potentially other osteoclast\u2010mediated bone diseases.<\/jats:p>","DOI":"10.1002\/ptr.7088","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T01:24:10Z","timestamp":1616981050000},"page":"3821-3835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Protocatechualdehyde inhibits<scp>receptor activator of nuclear factor kappa\u2010B ligand<\/scp>\u2010induced osteoclastogenesis and attenuates lipopolysaccharide\u2010induced inflammatory osteolysis"],"prefix":"10.1002","volume":"35","author":[{"given":"Hao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine) Shaoxing 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