title: Ethyl-2, 5-dihydroxybenzoate displays dual activity by promoting osteoblast differentiation and inhibiting osteoclast differentiation.
abstract: The interplay between bone-forming osteoblasts and bone-resorbing osteoclasts is essential for balanced bone remodeling. In this study, we evaluate the ability of ethyl-2, 5-dihyrdoxybenzoate (E-2, 5-DHB) to affect both osteoblast and osteoclast differentiation for bone regeneration. Osteogenic differentiation of human mesenchymal stem cells (hMSCs) was quantified by measuring alkaline phosphatase (ALP) activity and calcium deposition. To evaluate osteoclast differentiation, we investigated the effect of E-2, 5-DHB on RANKL-activated osteoclastogenesis in RAW 264.7 cells. E-2, 5-DHB enhanced ALP activity and inhibited RAW 264.7 cell osteoclastogenesis in vitro. To assess the in vivo activity of E-2, 5-DHB, hMSCs were delivered subcutaneosuly alone or in combination with E-2, 5-DHB in an alginate gel into the backs of nude-mice. Histological and immunohistochemical evaluation showed significantly higher calcium deposition in the E-2, 5-DHB group. Osteocalcin (OCN) was highly expressed in cells implanted in the gels containing E-2, 5-DHB. Our results suggest that E-2, 5-DHB can effectively enhance osteoblast differentiation and inhibit osteoclast differentiation both in vitro and in vivo. Understanding the dual function of E-2, 5-DHB on osteoblast and osteoclast differentiation will aid in future development of E-2, 5-DHB as a material for bone tissue engineering.
authors: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors: Byeong-Ju
authors: BJ
authors: Kwon
authors: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors: Mi Hee
authors: MH
authors: Lee
authors: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors: Min-Ah
authors: MA
authors: Koo
authors: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors: Min Sung
authors: MS
authors: Kim
authors: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors: Gyeung Mi
authors: GM
authors: Seon
authors: Cellsafe Ltd., 119 Ajou University Industry Cooperation Foundation, Suwon 442-749, Republic of Korea.
authors: Jae-Jin
authors: JJ
authors: Han
authors: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea. Electronic address: parkjc@yuhs.ac.
authors: Jong-Chul
authors: JC
authors: Park
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062385:Hydroxybenzoates / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D000067996:RAW 264.7 Cells
chemical_list: D062385:Hydroxybenzoates; C452809:ethyl 2,4-dihydroxybenzoate
keywords: Bone formation; Bone remodeling; Bone tissue engineering; Ethyl-2, 5-dihyrdoxybenzoate; Osteoblast differentiation; Osteoclast differentiation