Effects of Curcumin on the Proliferation and Mineralization of Human Osteoblast-Like Cells: Implications of Nitric Oxide

Abstract

Curcumin (diferuloylmethane) is found in the rhizomes of the turmeric plant (Curcuma longa L.) and has been used for centuries as a dietary spice and as a traditional Indian medicine used to treat different conditions. At the cellular level, curcumin modulates important molecular targets: transcription factors, enzymes, cell cycle proteins, cytokines, receptors and cell surface adhesion molecules. Because many of the curcumin targets mentioned above participate in the regulation of bone remodeling, curcumin may affect the skeletal system. Nitric oxide (NO) is a gaseous molecule generated from l-arginine during the catalization of nitric oxide synthase (NOS), and it plays crucial roles in catalization and in the nervous, cardiovascular and immune systems. Human osteoblasts have been shown to express NOS isoforms, and the exact mechanism(s) by which NO regulates bone formation remain unclear. Curcumin has been widely described to inhibit inducible nitric oxide synthase expression and nitric oxide production, at least in part via direct interference in NF-κB activation. In the present study, after exposure of human osteoblast-like cells (MG-63), we have observed that curcumin abrogated inducible NOS expression and decreased NO levels, inhibiting also cell prolifieration. This effect was prevented by the NO donor sodium nitroprusside. Under osteogenic conditions, curcumin also decreased the level of mineralization. Our results indicate that NO plays a role in the osteoblastic profile of MG-63 cells.

Attenuation of hind-limb suspension-induced bone loss by curcumin is associated with reduced oxidative stress and increased vitamin D receptor expression

“…Some reports have reported that curcumin at high concentration (>10 μM) markedly inhibited the proliferation of rat calvarial osteoblastic cells and induced the death of human osteoblasts [20][21][22]. Gu et al demonstrated that curcumin (10 μM) promoted rat mesenchymal stem cell osteoblast differentiation by upregulation of HO-1 [23].…”

Role of Curcumin in Common Musculoskeletal Disorders: a Review of Current Laboratory, Translational, and Clinical Data

“…Curcumin can improve multiple aspects of bone health in subjects with osteoporosis by acting on multiple steps in the activation and differentiation of osteoclasts, improving mineral density and mechanical properties. Mechanisms that have been proposed include inhibition of NF-κB, RANKL, NO production, generation of reactive oxygen species and inflammatory cytokine synthesis [36][37][38][39][40][41][42][43] . Through these mechanisms, curcumin can decrease osteoclast number, differentiation and activation.…”

Attenuation of Oxidative Stress-Induced Osteoblast Apoptosis by Curcumin is Associated with Preservation of Mitochondrial Functions and Increased Akt-GSK3β Signaling

“…These findings suggest that curcumin affects the activity and number of osteoclasts, rather than osteoblasts, in the progression of bone loss associated with various pathological processes. Nonetheless, some studies have reported that high doses (>10 μM) of curcumin inhibit proliferation of rat calvarial osteoblasts and human osteoblast cell death [22][23][24]. Gu et al demonstrated that 10 μM curcumin promotes osteoblastic differentiation of rat mesenchymal stem cells by upregulation of HO-1 [25].…”