title: Osteoblast differentiation and bone formation gene expression in strontium-inducing bone marrow mesenchymal stem cell.
abstract: Osteoblastic differentiation from human mesenchymal stem cell (hMSCs) is an important step of bone formation. We studied the in vitro induction of hMSCs by using strontium ranelate, a natural trace amount in water, food and human skeleton. The mRNA synthesis of various osteoblast specific genes was assessed by means of reverse transcription polymerase chain reaction (RT-PCR). In the hMSCs culture, strontium ranelate could enhance the induction of hMSCs to differentiate into osteoblasts. Cbfa1 gene was earlier expressed on day 4 of cell culture (the control group, on day 14) and osteonectin on day 11 (control, on day 21). The early Cbfa1 expression indicates that strontium could enhance osteoblastic differentiation. The detection of osteonectin using strontium induction indicates the role of strontium in enhancing bone remodeling, bone structure stabilization of hydroxyapatite molecule and collagen fibril organization. The cultured hMSCs in the presence of strontium expressed genes of bone extracellular matrix: collagen type I, bone sialoprotein and osteocalcin on the same days as control (same medium with no strontium). Concentration of strontium ranelate has been recommended to be optimized in between 0.2107 - 21.07 microg/ml whereas the high concentration up to 210.7 microg/ml have delayed effect on osteoblastic differentiation with delayed expression on Cbfa1 and osteonectin, and inhibitory effect on bone sialoprotein expression. In addition, strontium could help cell expansion by maintaining cell proliferation rate of hMSCs and osteoblast lineage. We recommend that the strontium is an important factor for inducing mesenchymal stem cells to differentiate into osteoblasts with further enhancement on bone formation. This model might provide a useful cell source for tissue engineering and bone repair.
authors.affiliation: Cell Engineering and Tissue Growth Laboratory, Institute of Science and Technology for Research and Development, Mahidol University, Phuttamonthon Salaya, Nakhonpathom 73170, Thailand.
authors.forename: Monnipha
authors.initials: M
authors.lastname: Sila-Asna
authors.forename: Ahnond
authors.initials: A
authors.lastname: Bunyaratvej
authors.forename: Sakan
authors.initials: S
authors.lastname: Maeda
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kitaguchi
authors.forename: Narong
authors.initials: N
authors.lastname: Bunyaratavej
mesh_terms: D001854:Bone Marrow Cells / Q000187:drug effects*; D002454:Cell Differentiation / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics*; D053495:Osteopontin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013324:Strontium / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; D015675:Osteocalcin; D053495:Osteopontin; D013324:Strontium