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RISS 인기검색어
- 검색키워드
- 저자 : David William Green (검색결과 5 건)
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Osteogenic Potency of Nacre on Human Mesenchymal Stem Cells
GREEN DAVID WILLIAM,정한성,권혁재 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.3
Nacre seashell is a natural osteoinductive biomaterial with strong effects on osteoprogenitors, osteoblasts, and osteoclasts during bone tissue formation and morphogenesis. Although nacre has shown, in one study, to induce bridging of new bone across large non-union bone defects in 8 individual human patients, there have been no succeeding human surgical studies to confirm this outstanding potency. But the molecular mechanisms associated with nacre osteoinduction and the influence on bone marrow-derived mesenchymal stem cells (BMSC’s), skeletal stem cells or bone marrow stromal cells remain elusive. In this study we highlight the phenotypic and biochemical effects of Pinctada maxima nacre chips and the global nacre soluble protein matrix (SPM) on primary human bone marrowderived stromal cells (hBMSCs) in vitro. In static co-culture with nacre chips, the hBMSCs secreted Alkaline phosphatase (ALP) at levels that exceeded bone morphogenetic protein (rhBMP-2) treatment. Concentrated preparation of SPM applied to Stro-1 selected hBMSC’s led to rapid ALP secretions, at concentrations exceeding the untreated controls even in osteogenic conditions. Within 21 days the same population of Stro-1 selected hBMSCs proliferated and secreted collagens I-IV, indicating the premature onset of an osteoblast phenotype. The same SPM was found to promote unselected hBMSC differentiation with osteocalcin detected at 7 days, and proliferation increased at 7 days in a dose-dependent manner. In conclusion, nacre particles and nacre SPM induced the early stages of human bone cell differentiation, indicating that they may be promising soluble factors with osteoinductive capacity in primary human bone cell progenitors such as, hBMSC’s.
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A model system for polydactyly; The Korean Ogye
김은정,김재우,David William Green,정한성 대한구강해부학회 2015 대한구강해부학회지 Vol.36 No.1
Polydactyly, the addition of one or more extra digits, occurs in various vertebrates as well as in humans with prevalence ranging from 5 to 19 per 10,000 live births1,2). This common malformation has a genetic cause and was one of the earliest genetic mutations studied in chicken3). Furthermore, polydactyly relates to the phenotype found in many domestic chicken breeds including Dorking, Silkie, and Sultan. Autosomal inheritance is shown in polydactyly of chicken with incomplete penetrance 4). One proposal is that it is controlled by more than one gene5). Sonic hedgehog (Shh) is a principal master regulator determining the digit number and identity in the vertebrate limbs. Shh is expressed in posterior region of mesenchyme, known as the zone of polarizing activity (ZPA) in the limb bud. Shh is a key morphogen at the anterior-posterior limb axis in early embryogenesis6,7). Intrinsic regions of Lmbr1 (a ZPA regulatory sequence, ZRS), which is located 1Mb upstream of Shh, regulate Shh expression in the ZPA. Mutations in intron3 of LMBR1 are associated with ectopic Shh expression in the limb and / or polydactyly in chickens7-10). Along with this, deletion of intron 5 of LMBR1 (1654 bp) causes oligozeugodactyly (loss of posterior element of zeugopod along with all digits except digit1 in the leg) for Silkie11). The Silkie has polydactylous feet and expresses ectopic Shh as well as the expression of genes downstream of Shh signaling, Hoxd13 and Bmp2, in the anterior leg bud from stage 25 Hamburger and Hamilton (HH) stages12). Korean Ogye, which has been mis-named as Korean Native Ogol chickens, is a species protected by the Korean government (Protected Species Act No. 265), and has been studied at genetic and population levels13-15). Korean Ogye has black feathers, as well as black bones, skin, eye, and claws. It has been known that purebred of Korean Ogye has four toes with no fine furs, whereas mixed Korean Ogye expresses polydactyly with 5-6 toes with fine furs. This study aims to reveal the phenotype and genetic expressions related to Korean Ogye polydactyly.
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Qing Ge,David William Green,이동준,김현이,Zhengguo Piao,이종민,정한성 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.12
Regenerative orthopedics needs significant devices to transplant human stem cells into damaged tissue and encourage automatic growth into replacements suitable for the human skeleton. Soft biomaterials have similarities in mechanical, structural and architectural properties to natural extracellular matrix (ECM), but often lack essential ECM molecules and signals. Here we engineer mineralized polysaccharide beads to transform MSCs into osteogenic cells and osteoid tissue for transplantation. Bone morphogenic proteins (BMP-2) and indispensable ECM proteins both directed differentiation inside alginate beads. Laminin and collagen IV basement membrane matrix proteins fixed and organized MSCs onto the alginate matrix, and BMP-2 drove differentiation, osteoid tissue self-assembly, and small-scale mineralization. Augmentation of alginate is necessary, and we showed that a few rationally selected small proteins from the basement membrane (BM) compartment of the ECM were sufficient to upregulate cell expression of Runx-2 and osteocalcin for osteoid formation, resulting in Alizarin red-positive mineral nodules. More significantly, nested BMP-2 and BM beads added to a non-union skull defect, self-generated osteoid expressing osteopontin (OPN) and osteocalcin (OCN) in a chain along the defect, at only four weeks, establishing a framework for complete regeneration expected in 6 and 12 weeks. Alginate beads are beneficial surgical devices for transplanting therapeutic cells in programmed (by the ECM components and alginate-chitosan properties) reaction environments ideal for promoting bone tissue.
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