title: Ferulic acid impairs osteoclast fusion and exacerbates survival of mature osteoclasts.
abstract: Elevated bone loss induced by osteoclasts is a critical and most commonly observed pathological complication during osteolytic diseases such as osteoporosis. Hence, attenuation of osteoclast formation or function is a classical therapeutic approach to regulate bone loss. In this study, we found that ferulic acid (FA), a natural compound potently inhibited osteoclast formation in human CD14+ peripheral blood monocytes ex vivo with an IC50 of 39 µM. Moreover, due to impaired differentiation of osteoclast progenitors, actin ring formation and bone resorption activity were also perturbed. Investigation of underlying molecular mechanisms revealed that FA inhibited the RANKL-induced expression of dendritic cell-specific transmembrane protein (DC-STAMP), a critical regulator of osteoclast fusion. In addition, expression of matrix metalloproteinase-9 (MMP-9) and cathepsin K, the key osteoclast specific lysosomal proteases involved in bone matrix resorption were severely aggravated by FA. A significant reduction in mature osteoclast numbers was detected in the presence of FA accompanied by increased caspase-3 activity and DNA-fragmentation, a characteristic hallmark of apoptosis. Collectively, these results suggested that FA inhibited osteoclast fusion by suppressing the expression of DC-STAMP and induced apoptosis in mature osteoclasts by the caspase-3 pathway.
authors.affiliation: Department of Physiology, University of Pretoria, Private Bag X323, Arcadia, 0007, Pretoria, South Africa.
authors.forename: Travers
authors.initials: T
authors.lastname: Sagar
authors.affiliation: Department of Physiology, University of Pretoria, Private Bag X323, Arcadia, 0007, Pretoria, South Africa.
authors.forename: Mpho
authors.initials: M
authors.lastname: Rantlha
authors.affiliation: School of Food and Nutrition, Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand.|Department of Human Nutrition, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.|Associate of the Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria, South Africa.
authors.forename: Marlena C
authors.initials: MC
authors.lastname: Kruger
authors.affiliation: Department of Physiology, University of Pretoria, Private Bag X323, Arcadia, 0007, Pretoria, South Africa. magdalena.coetzee@up.ac.za.|Associate of the Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria, South Africa. magdalena.coetzee@up.ac.za.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Coetzee
authors.affiliation: Department of Physiology, University of Pretoria, Private Bag X323, Arcadia, 0007, Pretoria, South Africa. vishwa.deepak@nuigalway.ie.
authors.forename: Vishwa
authors.initials: V
authors.lastname: Deepak
keywords: Bone; Menopause; Osteoclast; Osteolysis; RANKL