Melatonin at Pharmacologic Doses Increases Bone Mass by Suppressing Resorption Through Down-Regulation of the RANKL-Mediated Osteoclast Formation and Activation

Koyama, Hiroki; Nakade, Osamu; Takada, Yukihiro; Kaku, Tohru; Lau, K.-H. William

doi:10.1359/jbmr.2002.17.7.1219

Cited by 241 publications

(287 citation statements)

References 47 publications

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“…Moreover, in vitro studies showed that melatonin is capable of promoting osteoblast proliferation directly and stimulating these cells to produce increased amounts of several bone matrix proteins such as bone sialoprotein, alkaline phosphatase, osteocalcin (Roth et al 1999) and procollagen type I c-peptide (Nakade et al 1999), responsible for bone formation. Osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts is also increased by melatonin in vitro (Koyama et al 2002). This data may support the radioprotective effect of melatonin on bone growth.…”

Section: Radioprotective Effect Of Melatonin and Its Metabolitessupporting

confidence: 60%

Melatonin for Protection Against Ionizing Radiation

El-Missiry¹,

Othman²,

Al-Abdan³

2012

Current Topics in Ionizing Radiation Research

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Section: Radioprotective Effect Of Melatonin and Its Metabolitessupporting

confidence: 60%

Melatonin for Protection Against Ionizing Radiation

El-Missiry¹,

Othman²,

Al-Abdan³

2012

Current Topics in Ionizing Radiation Research

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“…Melatonin is believed to promote bone mass by increasing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts [54], promoting osteoblast proliferation [40] and reducing osteoblast RANKL expression [28]. In animal models of idiopathic scoliosis, such as the chick experimental pinealectomy model, the development of idiopathic scoliosis-like changes has been associated with reduced levels of serum melatonin.…”

Section: Intrinsic Factors Of the Ais Spinal Musculoskeletal System Smentioning

confidence: 99%

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Ede

Jones

2016

International Orthopaedics (SICOT)

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Adolescent idiopathic scoliosis (AIS) is now considered to be a multifactorial heterogeneous disease, with recent genomic studies supporting the role of intrinsic factors in contributing to the onset of disease pathology and curve progression. Understanding the key molecular signalling pathways by which these intrinsic factors mediate AIS pathology may facilitate the development of pharmacological therapeutics and the identification of predictive markers of progression. The heterogenic nature of AIS has implicated multiple tissue types in the disease pathophysiology, including spinal bone, intervertebral disc and paraspinal muscles. In this review, we highlight some of the mechanisms and intrinsic molecular regulators within these different tissue types and review the evidence for their involvement in AIS pathology.

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“…In addition, dietary and endogenous antioxidants were markedly decreased in osteoporotic women (Maggio et al 2003). Furthermore, the administration of various natural or synthetic antioxidants, such as vitamins C and E (Leveille et al 1997, Wang et al 1997, Hall & Greendale 1998, Melhus et al 1999, N-acetyl cysteine (Lean et al 2003), melatonin (Koyama et al 2002) and dietary flavonoids , has been shown to be of benefit in the prevention and/or attenuation of osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells

Koh

Lee²,

Byun³

et al. 2005

Journal of Endocrinology

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Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although -lipoic acid ( -LA) has been shown to act as a thiol antioxidant, its effect on bone cells has not been determined. Using proteomic analysis, we identified six differentially expressed proteins in the conditioned media of -LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor B ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that -LA stimulated RANKL production in cellular extracts (membranous RANKL) about 5-fold and in conditioned medium (soluble RANKL) about 23-fold, but had no effect on osteoprotegerin (OPG) secretion. Despite increasing the RANKL/OPG ratio, -LA showed a dose-dependent suppression of osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts and in a mouse bone marrow cell culture system, and reduced bone resorption in a dose-dependent manner. In addition, -LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by -LA without any posttranslational processing. In contrast, -LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that -LA suppresses osteoclastogenesis by directly inhibiting RANKL-RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that -LA-induced soluble RANKL is not produced by shedding of membranous RANKL.

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Melatonin at Pharmacologic Doses Increases Bone Mass by Suppressing Resorption Through Down-Regulation of the RANKL-Mediated Osteoclast Formation and Activation

Cited by 241 publications

References 47 publications

Melatonin for Protection Against Ionizing Radiation

Melatonin for Protection Against Ionizing Radiation

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells

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