Differential Expression of Adhesion-Related Proteins and MAPK Pathways Lead to Suitable Osteoblast Differentiation of Human Mesenchymal Stem Cells Subpopulations

Abstract

Cellular adhesion enables communication between cells and their environment. Adhesion can be achieved throughout focal adhesions and its components influence osteoblast differentiation of human mesenchymal stem cells (hMSCs). Because cell adhesion and osteoblast differentiation are closely related, this article aimed to analyze the expression profiles of adhesion-related proteins during osteoblastic differentiation of two hMSCs subpopulations (CD105(+) and CD105(-)) and propose a strategy for assembling bone grafts based on its adhesion ability. In vitro experiments of osteogenic differentiation in CD105(-) cells showed superior adhesion efficiency and 2-fold increase of α-actinin expression compared with CD105(+) cells at the maturation stage. Interestingly, levels of activated β1-integrin increased in CD105(-) cells during the process. Additionally, the CD105(-) subpopulation showed 3-fold increase of phosphorylated FAK(Y397) compared to CD105(+) cells. Results also indicate that ERK1/2 was activated during CD105(-) bone differentiation and participation of mitogen-activated protein kinase (MAPK)-p38 in CD105(+) differentiation through a focal adhesion kinase (FAK)-independent pathway. In vivo trial demonstrated that grafts containing CD105(-) showed osteocytes embedded in a mineralized matrix, promoted adequate graft integration, increased host vascular infiltration, and efficient intramembranous repairing. In contrast, grafts containing CD105(+) showed deficient endochondral ossification and fibrocartilaginous tissue. Based on the expression of α-actinin, FAKy,(397) and ERK1/2 activation, we define maturation stage as critical for bone graft assembling. By in vitro assays, CD105(-) subpopulation showed superior adhesion efficiency compared to CD105(+) cells. Considering in vitro and in vivo assays, this study suggests that integration of a scaffold with CD105(-) subpopulation at the maturation stage represents an attractive strategy for clinical use in orthopedic bioengineering.

Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells

“…Indeed, CD105 high MSCs were shown to differentiate more effectively into chondrocytes compared to CD105 low MSCs [28]. Moreover, hMSCs expressing low CD105 exhibited increased osteogenic gene expression and were more prone to osteogenic differentiation [6,29]. In agreement with these studies, the present study revealed that CD105 low population of hMSCs induced by long-term MC-A-treatment exhibited reduced chondrogenic differentiation potential.…”

Immortalizing Mesenchymal Stromal Cells from Aged Donors While Keeping Their Essential Features

“…However, it has been noted that CD105 + MSCs have no superior chondrogenic potential than the CD105ones [68], even though it is still controversial [69]. It has also been stated that, as a counterpart of decreased chondrogenic potential, CD105 -MSCs show increased osteogenic potential [69] as a result of superior adhesion and mineralization efficiency [70], which might be related to the superior osteogenic potential of iMSCs. Nevertheless, surface marker expression does not necessarily reflect the functional capacities of MSC [63], and the inferior osteogenic potential of primary MSC#6 may be also due to them being differentiated at the 6th passage, when cells are expected to be aged [5,71].…”

Stem cell therapy for treating osteonecrosis of the femoral head: From clinical applications to related basic research

“…Furthermore, through in vivo trials, it was demonstrated that grafts containing CD105- cells promoted adequate graft integration, improved host vascular infiltration, and facilitated efficient repair through intramembranous ossification. By contrast, grafts containing CD105+ cells showed abundant fibrocartilaginous tissue and deficient endochondral ossification [ 67 ].…”