Abstract
BackgroundAs the representative of fenamic acids, an important group of NSAIDs, flufenamic acid (FFA) has been used for anti-inflammation and analgesia in the clinic. Recently, researches have focused on the role of some members of NSAIDs in promoting osteogenesis. However, little attention has been paid to the subgroup of fenamic acids, and it remains unclear whether FFA and other fenamic acids could regulate mesenchymal stem cells’ (MSCs) lineage commitment and bone regeneration.MethodsHere we treated two kinds of human MSCs with FFA at different concentrations in vitro and examined the effect of FFA on osteogenic differentiation of human MSCs. This was followed by heterotopic bone formation assay in nude mice. In addition, ovariectomized and aged mice were used as osteoporotic models to test the effect of FFA on osteoporosis. Besides, activators and inhibitor of nuclear factor-κB (NF-κB) signaling pathway and western blot were used to clarify the mechanism of the promoting effect of low concentration FFA on osteogenesis.ResultsOur results indicated that low concentrations of FFA could significantly enhance osteogenic differentiation of human MSCs in vitro, as well as in vivo. In addition, FFA treatment suppressed bone loss in ovariectomized and aged mice. Mechanistically, FFA at low concentrations promoted osteogenesis differentiation of human MSCs by inhibition of the NF-κB signaling pathway.ConclusionsCollectively, our study suggested that low concentration FFA could be used in bone tissue engineering or osteoporosis by promoting osteogenic differentiation of human MSCs.
Highlights
As the representative of fenamic acids, an important group of Non-steroidal anti-inflammatory drugs (NSAIDs), flufenamic acid (FFA) has been used for anti-inflammation and analgesia in the clinic
Our results demonstrated that low concentration FFA promoted osteogenic differentiation of hMSCs in vitro and the effect declined with the concentration increasing
FFA at low concentrations promoted osteogenic differentiation of hBMMSCs in vitro alkaline phosphatase (ALP) staining and quantification showed that low concentration FFA promoted the osteogenic differentiation of hBMMSCs cultured in OM on day 7 (Fig. 1a, c)
Summary
As the representative of fenamic acids, an important group of NSAIDs, flufenamic acid (FFA) has been used for anti-inflammation and analgesia in the clinic. As a common disease that can often be seen in the clinic, osteoporosis brings health and economic burdens to patients and remains a clinical challenge It is usually caused by estrogen deficiency in menopausal women or by aging. The members of the NSAIDs are quite different in their chemical structures and other properties, which may cause different effects in addition to anti-inflammatory and analgesia effects. According to their chemical structure, NSAIDs can be divided into several groups, for instance, salicylic acids, anilines, acetic acids, oxicams, and fenamic acids [9]. The effect of fenamic acids on MSC fate has not been reported
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