Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss

Abstract

Osteoporosis is a common metabolic bone disease with a rapidly increasing prevalence, characterized by massive bone loss because of excessive osteoclast formation. Gallic acid (GA), a phenolic acid isolated from Cornus officinalis, has anti-inflammatory and anti-oxidant effects, but its effect on osteoclast formation has not been confirmed. In our study, we demonstrated that GA significantly inhibited RANKL‐induced osteoclast formation and function of osteoclast in bone marrow monocytes (BMMs) and RAW264.7 cells in a dose-dependent manner without cytotoxicity. For molecular mechanisms, GA repressed osteoclastogenesis by blocking Akt, ERK, and JNK pathways, and suppressed osteoclastogenesis-related marker expression, including nuclear factor of the activated T-cell cytoplasmic 1 (NFATc1), c‐Fos, and cathepsin K (CTSK). In addition, we further assessed the effect of GA in an ovariectomized mouse model, which indicated that GA has a notable effect on preventing bone loss. In conclusion, GA exerts notable effects in inhibiting osteoclastogenesis and preventing ovariectomy-induced bone loss, suggesting that GA is a potential agent in osteoporosis treatment.

Gallic acid induces osteoblast differentiation and alleviates inflammatory response through GPR35/GSK3β/β‐catenin signaling pathway in human periodontal ligament cells

“…27 GA exerts notable effects in inhibiting osteoclastogenesis and preventing ovariectomy-induced bone loss. 28 GA administration improved periodontal health in Wistar rats by reducing alveolar bone loss, and periodontal inflammation and increasing osteoblastic activity 29 ; however, the underlying mechanism in in vitro model is still not clear. In this study, GA promoted hPDL cell differentiation into osteoblast activity as well as inhibited Pg-LPS induce inflammation, ROS production by GSK3β/β-catenin signaling pathway.…”

“…Bone metabolism is a consecutive cycle of bone formation and resorption that is carefully orchestrated by the dynamic relationship between osteoclasts, osteoblasts and an array of hormonal and regulatory influences 27 . GA exerts notable effects in inhibiting osteoclastogenesis and preventing ovariectomy‐induced bone loss 28 . GA administration improved periodontal health in Wistar rats by reducing alveolar bone loss, and periodontal inflammation and increasing osteoblastic activity 29 ; however, the underlying mechanism in in vitro model is still not clear.…”

Effect of Steamed Stauntonia hexaphylla fruit on RAW 264.7 osteoclast and MC3T3-E1 osteoblast differentiation

“…Therefore, the authors concluded that 5-HMF, which was signi cantly increased during the steaming process of SHF, may be a cause of the increase in osteogenic activity. 5-HMF is widely available in different food products which are thermally processed and it serves as a well-established indicator of nonenzymic browning, frequently employed to assess deteriorative changes resulting from heating and/or prolonged storage of food products [41]. It exhibits biphasic effects, positive and negative activities in biological systems.…”

Plant molecules reinforce bone repair: Novel insights into phenol-modified bone tissue engineering scaffolds for the treatment of bone defects

“…An additional strategy for interdicting osteoclastogenesis is to interfere the combination of RANKL and RANK [ 86 ]. The AKT/ERK/JNK axis was the downstream signaling pathway of RANK/RANKL [ 87 ]. The administration of GA has been confirmed to hinder the RANKL-induced osteoclastogenesis via inhibiting the AKT/ERK/JNK pathway, suggesting that it could be a potential drug for bone regeneration [ 87 ].…”