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Seoul, South Korea

Cho E.-S.,Chonbuk National University | Kim M.-K.,Chonbuk National University | Son Y.-O.,University of Kentucky | Lee K.-S.,Korea Bone Bank Co | And 3 more authors.
Molecules and Cells | Year: 2012

Rosiglitazone has the potential to activate peroxisome proliferator- activated receptor-γ (PPARγ), which in turn can affect bone formation and resorption. However, the mechanisms by which rosiglitazone regulates osteoclastic or osteoblastic differentiation are not fully understood. This study examines how rosiglitazone affects osteoclast formation, bone resorption and osteoblast differentiation from mouse bone marrow. Rosiglitazone treatment not only inhibited the formation of tartrate-resistant acid phosphatase-positive cells, but also prevented pit formation by bone marrow cells in a dose- and time-dependent manner. Rosiglitazone also suppressed the receptor activator of nuclear factor (NF)-κB ligand (RANKL) receptor (RANK) expression but increased PPARγ2 expression in the cells. In addition, rosiglitazone diminished RANKL-induced activation of NF-κB-DNA binding by blocking IκBα phosphorylation. Furthermore, it reduced collagen and osteocalcin levels to nearly zero and prevented mRNA expression of osteoblast-specific proteins including runtrelated transcription factor-2, osteocalcin, and type I collagen. However, mRNA levels of adipocyte-specific marker, aP2, were markedly increased in the cells co-incubated with rosiglitazone. These results suggest that PPARγ activation by rosiglitazone inhibits osteoblast differentiation with increased adipogenesis in bone marrow cells and also may prevent osteoclast formation and bone resorption in the cells. © 2012 KSMCB. Source

Joung Y.H.,Konkuk University | Lim E.J.,Konkuk University | Darvin P.,Konkuk University | Chung S.C.,Konkuk University | And 6 more authors.
PLoS ONE | Year: 2012

Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities. But, its effects on bone are unknown. Growth hormone (GH) is regulator of bone growth and bone metabolism. GH activates several signaling pathways such as the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) pathway, thereby regulating expression of genes including insulin-like growth factor (IGF)-1. GH exerts effects both directly and via IGF-1, which signals by activating the IGF-1 receptor (IGF-1R). In this study, we investigated the effects of MSM on the GH signaling via the Jak/STAT pathway in osteoblasts and the differentiation of primary bone marrow mesenchymal stem cells (MSCs). MSM was not toxic to osteoblastic cells and MSCs. MSM increased the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and MSCs. MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. We found that MSM and GH, separately or in combination, activated GH signaling via the Jak2/STAT5b pathway in UMR-106 cells. Using siRNA analysis, we found that STAT5b plays an essential role in GH signaling activation in C3H10T1/2 cells. Osteogenic marker genes (ALP, ON, OCN, BSP, OSX, and Runx2) were activated by MSM, and siRNA-mediated STAT5b knockdown inhibited MSM-induced expression of osteogenic markers. Furthermore, MSM increased ALP activity and the mineralization of MSCs. Taken together, these results indicated that MSM can promote osteogenic differentiation of MSCs through activation of STAT5b. © 2012 Joung et al. Source

Lee S.-Y.,Chonbuk National University | Lee K.-S.,Chonbuk National University | Lee K.-S.,Korea Bone Bank Co | Yi S.H.,Chonbuk National University | And 2 more authors.
PLoS ONE | Year: 2013

Numerous studies have reported that inflammatory cytokines are important mediators for osteoclastogenesis, thereby causing excessive bone resorption and osteoporosis. Acteoside, the main active compound of Rehmannia glutinosa, which is used widely in traditional Oriental medicine, has anti-inflammatory and antioxidant potentials. In this study, we found that acteoside markedly inhibited osteoclast differentiation and formation from bone marrow macrophages (BMMs) and RAW264.7 macrophages stimulated by the receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). Acteoside pretreatment also prevented bone resorption by mature osteoclasts in a dose-dependent manner. Acteoside (10 μM) attenuated RANKL-stimulated activation of p38 kinase, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, and also suppressed NF-κB activation by inhibiting phosphorylation of the p65 subunit and the inhibitor κBα. In addition, RANKL-mediated increases in the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and in the production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were apparently inhibited by acteoside pretreatment. Further, oral acteoside reduced ovariectomy-induced bone loss and inflammatory cytokine production to control levels. Our data suggest that acteoside inhibits osteoclast differentiation and maturation from osteoclastic precursors by suppressing RANKL-induced activation of mitogen-activated protein kinases and transcription factors such as NF-κB, c-Fos, and NFATc1. Collectively, these results suggest that acteoside may act as an anti-resorptive agent to reduce bone loss by blocking osteoclast activation. © 2013 Lee et al. Source

Kim J.-W.,Yonsei University | Jeong I.-H.,Inha University | Lee K.-I.,Korea Bone Bank Co | Jung U.-W.,Yonsei University | And 4 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2012

Block-type biphasic calcium phosphate (BCP) carriers are more effective at delivering recombinant human bone morphogenetic protein-2 (rhBMP-2) in various clinical situations than are particle-type carriers, due to their potential for highly successful three-dimensional bone regeneration. The aim of this study was to confirm the boneregenerative capabilities of three-dimensional BCP blocks with a low hydroxyapatite/β-tricalcium phosphate ratio (20/80) combined with collagen (10% wt) as an rhBMP-2 delivery system in a craniofacial vertical bone augmentation model. BCP blocks and BCP-collagen blocks (with average macropore sizes of 296 and 390 μm, respectively) with or without rhBMP-2 were fixed with osteosynthesis screws to the calvarial surface of rabbits. After 8 weeks, histologic and histomorphometric analyses were performed to evaluate the resulting new bone area, augmented area, bone density, and degree of integration. The area of new bone was significantly greater in specimens containing rhBMP-2 than in the control group (p< 0.05). Moreover, the area fractions of newly formed bone within the augmented area and a degree of integration between the regenerative bone and the calvarium were both significantly greater in the BCP-collagen/rhBMP-2 group than in the BCP/rhBMP-2 group (p< 0.05), whereas the two carrier systems exhibited similar rhBMP-2 release profiles, with sustained and linear release. The BCP and BCP/rhBMP-2 blocks exhibited excellent structural integrity, with large fragments of residual ceramic. In conclusion, the BCP-collagen composite block exhibited enhanced osteoinductive potential and could be a good candidate as a carrier of rhBMP-2 due to its characteristics of favorable volumetric stability, ease of handling, and excellent remodeling properties. © 2012 Wiley Periodicals, Inc. Source

Korea Bone Bank Co. | Date: 2010-05-12

The present invention relates to a method for purifying a protein belonging to the TGF-, superfamily, preferably BMP, and more preferably BMP-2. According to the invention, the number of purification steps is reduced and the purification process is simplified, compared to the conventional BMP-2 purification method. Thus, the time required for purification can be shortened and the cost can be reduced. In addition, the invention solves the problem that as the time for purification increases and the number of purification steps increases, BMP-2 is degraded by protease or lost during purification steps, resulting in a decrease in the final yield of BMP-2. Thus, the invention increases the final yield of BMP-2. In addition, according to the invention, although the number of purification steps is reduced, BMP-2 having high purity is obtained in high yield by optimizing and using filtrations and chromatographies, and columns, types and concentrations of buffers, and a cut-off size of membrane used in diafiltration, which are different from those of the conventional BMP-2 purification method.

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