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Alpha-lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio in human bone marrow stromal cells.
J Endocrinol. 2005 Jun; 185(3):401-13.JE

Abstract

Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although alpha-lipoic acid (alpha-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 alpha-LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor kappaB ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that alpha-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, alpha-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, alpha-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by alpha-LA without any posttranslational processing. In contrast, alpha-LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that alpha-LA suppresses osteoclastogenesis by directly inhibiting RANKL-RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that alpha-LA-induced soluble RANKL is not produced by shedding of membranous RANKL.

Authors+Show Affiliations

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15930166

Citation

Koh, Jung-Min, et al. "Alpha-lipoic Acid Suppresses Osteoclastogenesis Despite Increasing the Receptor Activator of Nuclear Factor kappaB Ligand/osteoprotegerin Ratio in Human Bone Marrow Stromal Cells." The Journal of Endocrinology, vol. 185, no. 3, 2005, pp. 401-13.
Koh JM, Lee YS, Byun CH, et al. Alpha-lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio in human bone marrow stromal cells. J Endocrinol. 2005;185(3):401-13.
Koh, J. M., Lee, Y. S., Byun, C. H., Chang, E. J., Kim, H., Kim, Y. H., Kim, H. H., & Kim, G. S. (2005). Alpha-lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio in human bone marrow stromal cells. The Journal of Endocrinology, 185(3), 401-13.
Koh JM, et al. Alpha-lipoic Acid Suppresses Osteoclastogenesis Despite Increasing the Receptor Activator of Nuclear Factor kappaB Ligand/osteoprotegerin Ratio in Human Bone Marrow Stromal Cells. J Endocrinol. 2005;185(3):401-13. PubMed PMID: 15930166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor kappaB ligand/osteoprotegerin ratio in human bone marrow stromal cells. AU - Koh,Jung-Min, AU - Lee,Young-Sun, AU - Byun,Chang-Hyun, AU - Chang,Eun-Ju, AU - Kim,Hyunsoo, AU - Kim,Yong Hee, AU - Kim,Hong-Hee, AU - Kim,Ghi Su, PY - 2005/6/3/pubmed PY - 2005/7/21/medline PY - 2005/6/3/entrez SP - 401 EP - 13 JF - The Journal of endocrinology JO - J Endocrinol VL - 185 IS - 3 N2 - Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although alpha-lipoic acid (alpha-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 alpha-LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor kappaB ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that alpha-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, alpha-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, alpha-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by alpha-LA without any posttranslational processing. In contrast, alpha-LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that alpha-LA suppresses osteoclastogenesis by directly inhibiting RANKL-RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that alpha-LA-induced soluble RANKL is not produced by shedding of membranous RANKL. SN - 0022-0795 UR - https://www.unboundmedicine.com/medline/citation/15930166/Alpha_lipoic_acid_suppresses_osteoclastogenesis_despite_increasing_the_receptor_activator_of_nuclear_factor_kappaB_ligand/osteoprotegerin_ratio_in_human_bone_marrow_stromal_cells_ L2 - https://joe.bioscientifica.com/doi/10.1677/joe.1.05995 DB - PRIME DP - Unbound Medicine ER -