Anacardic acid-mediated regulation of osteoblast differentiation involves mitigation of inflammasome activation pathways
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Anacardic acid‑mediated regulation of osteoblast differentiation involves mitigation of inflammasome activation pathways Meera Venugopal1 · Jyotsna Nambiar1 · Bipin G. Nair1 Received: 19 July 2020 / Accepted: 10 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Disruption of the finely tuned osteoblast–osteoclast balance is the underlying basis of several inflammatory bone diseases, such as osteomyelitis, osteoporosis, and septic arthritis. Prolonged and unrestrained exposure to inflammatory environment results in reduction of bone mineral density by downregulating osteoblast differentiation. Earlier studies from our laboratory have identified that Anacardic acid (AA), a constituent of Cashew nut shell liquid that is used widely in traditional medicine, has potential inhibitory effect on gelatinases (MMP2 and MMP9) which are over-expressed in numerous inflammatory conditions (Omanakuttan et al. in Mol Pharmacol, 2012 and Nambiar et al. in Exp Cell Res, 2016). The study demonstrated for the first time that AA promotes osteoblast differentiation in lipopolysaccharide-treated osteosarcoma cells (MG63) by upregulating specific markers, like osteocalcin, receptor activator of NF-κB ligand, and alkaline phosphatase. Furthermore, expression of the negative regulators, such as nuclear factor-κB, matrix metalloproteinases (MMPs), namely MMP13, and MMP1, along with several inflammatory markers, such as Interleukin-1β and Nod-like receptor protein 3 were downregulated by AA. Taken together, AA expounds as a novel template for development of potential pharmacological therapeutics for inflammatory bone diseases. Keywords Osteoblast · Anacardic acid · Differentiation · Inflammasome · Osteomyelitis
Introduction Bone is a vigorous tissue that provides mechanical support, protection, and mobility in addition to being a storage site for minerals. Bone health chiefly depends on the mineral content in the bone, density, and the bone architecture [1]. A constant recycling of bone milieu leading to constitutive mineralization as well as resorption of bone is orchestrated by mainly two types of bone cells: osteoblasts that helps in bone mineralization and osteoclasts that assist in resorption of matrix. Synchronization of these processes which occurs as a result of balance between osteoblasts and osteoclasts is important in sustaining normal bone vigour, maturation, repair, and maintenance of calcium homeostasis [1, 2]. Imbalance of bone homeostasis, which is contributed to by several factors, results in prolonged survival and function of * Bipin G. Nair [email protected] 1
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, Kerala, India 690525
osteoclasts and reduced lifespan of osteoblasts, eventually leading to bone loss [3]. Inflammation has a profound effect on bone metabolism, with an uncontrolled inflammatory milieu known to reduce bone mineral density in numerous chronic inflammatory disease conditions, including osteomyelitis, osteoa
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