Immortalization of Human Marrow Stromal Cells by Retroviral Transduction With a Temperature Sensitive Oncogene: Identification of Bipotential Precursor Cells Capable of Directed Differentiation to Either an Osteoblast or Adipocyte Phenotype
| Autor: | Roslin Russell, B.M.J. Stringer, A. Houghton, Babatunde O. Oyajobi, G.A. Foster |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Histology Stromal cell Physiology Antigens Polyomavirus Transforming Endocrinology Diabetes and Metabolism Cellular differentiation Osteocalcin Cell Culture Techniques Adipose tissue Bone Marrow Cells Biology Dexamethasone Dinoprostone chemistry.chemical_compound Directed differentiation Calcitriol Internal medicine Adipocyte Adipocytes Cyclic AMP medicine Humans Glucocorticoids Aged DNA Primers Osteoblasts Cell Differentiation Osteoblast Alkaline Phosphatase Cell Transformation Viral Hematopoietic Stem Cells Immunohistochemistry Extracellular Matrix Up-Regulation Cell biology Phenotype medicine.anatomical_structure Endocrinology chemistry Parathyroid Hormone Cell culture Female Bone marrow Stromal Cells Procollagen |
| Zdroj: | Bone. 22:7-16 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/s8756-3282(97)00229-9 |
| Popis: | The etiology of osteoporosis is multifactorial, but there is evidence from both animal and human studies that the volume of marrow adipose tissue increases when bone volume is reduced in osteoporosis. The cell-related mechanism that may account for this inverse relationship between the volume of marrow adipose tissue and bone remains to be clarified, although it is known that both adipocytes and osteoblasts are derived from stromal cell precursors in bone marrow. We report that retroviral transduction with a temperature-sensitive oncogene (SV40 large T antigen) can generate bipotential cell lines from human marrow stroma that are capable of directed differentiation, in vitro, down either an osteogenic or adipocytic lineage pathway. One such clone, designated hOP 7, expresses type α1(I) procollagen and has low alkaline phosphatase (AP) activity under basal culture conditions that is reminiscent of an osteoprogenitor cell. Exposure of hOP 7 cells to dexamethasone upregulates AP activity and enables the cells to mineralize their extracellular matrix. Also, treatment with calcitriol induces osteocalcin expression and both PTH and PGE 2 induce/augment cAMP formation. Incubation with normal rabbit serum, however, causes the cells to become adipogenic as demonstrated by histological staining with Oil-red-O, expression of mRNA for the early and late adipocyte markers lipoprotein lipase and glycerol 3-phosphate dehydrogenase, respectively, and loss of type α1(I) procollagen mRNA. The generation of homogeneous populations of these cells, as confirmed by Southern blot analysis, demonstrates the capacity of a human clonal cell line to differentiate in either an osteogenic or adipogenic direction. |
| Databáze: | OpenAIRE |
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