Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human bone marrow-derived mesenchymal stem cells (MSCs) represent an ideal source for cell therapy for inherited and degenerative diseases, bone and cartilage repair, and as target for gene therapy. The role of the combination of human parathyroid hormone (PTH) and vitamin D(3) in bone formation and mineralization has been established in several osteoblast cell culture studies. The aim of the present study was to evaluate the role of this hormonal combination alone and in the presence of bone morphogenetic protein-4 (BMP-4) or-6 (BMP-6) in inducing osteogenic differentiation of human MSC. Human MSC derived from adult normal bone marrow that are positive for CD29, CD44, CD105, and CD166 and negative for CD14, CD34, and CD45, were treated with the PTH and 1,25-dihydroxyvitamin D(3) in the presence and absence of recombinant human BMP-4 or BMP6. PTH and vitamin D(3) induced high levels of expression of two key markers of bone formation: osteocalcin and alkaline phosphatase by MSCs. BMP-6 but not BMP-4 increased osteocalcin expression induced by PTH and vitamin D(3). Both BMPs enhanced calcium formation in MSC cultures and this response was potentiated by PTH and vitamin D(3). The present results revealed a novel potent effect of PTH and vitamin D(3) plus BMPs in inducing bone development by human MSCs. These results may facilitate therapeutic utility of MSCs for bone disease and help clarify mechanisms involved in stem cell-mediated bone development.
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PMID:The role of BMP-6, IL-6, and BMP-4 in mesenchymal stem cell-dependent bone development: effects on osteoblastic differentiation induced by parathyroid hormone and vitamin D(3). 1518 23

Recently, research has focused on bone marrow derived multipotent mesenchymal precursor cells (MPC) and osteoblasts (OB) for clinical use in bone engineering. Prior to clinical application, cell based treatment concepts need to be evaluated in preclinical, large animal models. Sheep in particular are considered a valid model for orthopaedic and trauma related research. However, only sheep aged > 6 years show secondary osteon formation characteristic of human bone. Osteogenic cells isolated from animals of this age group remain poorly characterized. In the present study, ex vivo expanded MPC isolated from ovine bone marrow proliferated at a higher rate than OB derived from tibial compact bone as assessed in standard 2D cultures. MPC expressed the respective phenotypic profile typical for different mesenchymal cell populations (CD14(-)/CD31(-)/CD45(-)/CD29(+)/CD44(+)/CD166(+)) and showed a multilineage differentiation potential. When compared to OB, MPC had a higher mineralization potential under standard osteogenic culture conditions and expressed typical bone related markers such as osteocalcin, osteonectin and type I collagen at the mRNA and protein level. After 4 weeks in 3D culture, MPC constructs demonstrated higher cell density and mineralization, whilst cell viability on the scaffolds was assessed > 90%. Cells displayed a spindle-like morphology and formed interconnected networks. In contrast, when implanted subcutaneously into NOD/SCID mice, MPC presented a lower osteogenic potential than OB. In summary, this study provides a detailed characterisation of ovine MPC and OB from a bone engineering perspective and suggests that MPC and OB provide promising means for future bone disease related treatment applications.
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PMID:Ovine bone- and marrow-derived progenitor cells and their potential for scaffold-based bone tissue engineering applications in vitro and in vivo. 2056 83