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Osteoblast-Related Gene Expression of Bone Marrow Cells during the Osteoblastic Differentiation Induced by Type I Collagen

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2001

Year

TLDR

Bone marrow contains multipotent cells that differentiate into fibroblasts, adipocytes, and osteoblasts, and type I collagen’s Asp‑Gly‑Glu‑Ala domain engages the α2β1 integrin receptor to transmit extracellular signals. In this study, we investigated the expression of osteoblast‑related genes during osteoblastic differentiation induced by type I collagen. We cultured bone marrow cells on a type I collagen matrix and monitored the expression of alkaline phosphatase, osteocalcin, bone sialoprotein, osteopontin, and cbfa‑1 over time. Type I collagen matrix induced osteoblastic differentiation, leading to mineralized tissue formation after three weeks, with alkaline phosphatase and osteopontin expression rising over time, osteocalcin and bone sialoprotein appearing only after mineralization, cbfa‑1 expressed early, and blocking the collagen‑α2β1 integrin interaction with DGEA peptide suppressed osteoblastic phenotypes, underscoring this interaction as a critical differentiation signal.

Abstract

Bone marrow contains multipotent cells that differentiate into fibroblasts, adipocytes, and osteoblasts. Recently we found that type I collagen matrix induced the osteoblastic differentiation of bone marrow cells. Three weeks after cells were cultured with type I collagen, they formed mineralized tissues. In this study, we investigated the expression of osteoblast-related genes (alkaline phosphatase, osteocalcin, bone sialoprotein, osteopontin, and cbfa-1) during the osteoblastic differentiation. The expression of alkaline phosphatase and osteopontin genes increased time-dependently during the osteoblastic differentiation. Osteocalcin and bone sialoprotein genes were expressed in cells that formed mineralized tissues, and both were expressed only after cells reached the mineralized tissue-formation stage. On the other hand, the cbfa-1 gene was expressed from the early differentiation stage. The Asp-Gly-Glu-Ala (DGEA) amino acid domain of type I collagen interacts with the alpha2beta1 integrin receptor on the cell membrane and mediates extracellular signals into cells. When the collagen-integrin interaction was interrupted by the addition of DGEA peptide to the culture, the expression of osteoblastic phenotypes of bone marrow cells was inhibited. These findings imply that the collagen-alpha2beta1 integrin interaction is an important signal for the osteoblastic differentiation of bone marrow cells.