title: Homeobox B7 promotes the osteogenic differentiation potential of mesenchymal stem cells by activating RUNX2 and transcript of BSP.
abstract: Mesenchymal stem cells (MSCs) are a reliable cell source for tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. Here, we investigate HOXB7 function in the osteogenic differentiation potentials of MSCs using stem cells from apical papilla (SCAPs) and bone marrow stem cells (BMSCs). The HOXB7 gene is highly expressed in BMSCs compared with dental tissue-derived MSCs. We found that, in vitro, over-expression of HOXB7 in SCAPs enhanced alkaline phosphatase (ALP) activity and mineralization. HOXB7 over-expression affected the mRNA expression of osteonectin (ON), collagen alpha-2(I) chain (COL1A2), bone sialoprotein (BSP), and osteocalcin (OCN), led to the expression of the key transcription factor, runt-related transcription factor 2 (RUNX2), and promoted SCAP osteogenic differentiation in vitro. The knock-down of HOXB7 inhibited ALP activity, mineralization, and the expression of ON, BSP, COL1A2, OCN, and RUNX2 in BMSCs in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when HOXB7 was activated. Furthermore, Over-expression of HOXB7 significantly increased the levels of HOXB7 associated with the BSP promoter by ChIP assays. Taken together, these results indicate that HOXB7 enhances SCAP osteogenic differentiation by up-regulating RUNX2 and directly activating transcript of BSP. Thus, the activation of HOXB7 signaling might improve tissue regeneration mediated by MSCs. These results provide insight into the mechanism underlying the directed differentiation of MSCs.
authors.affiliation: Department of Stomatology, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Run-Tao
authors.initials: RT
authors.lastname: Gao
authors.affiliation: Department of Stomatology, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhan
authors.affiliation: Department of Stomatology, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Cen
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Stomatology, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
authors.forename: Shi-Min
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, Stomatological Hospita lof Nankai University Tianjin 300041, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yao
authors.affiliation: Institute of Biophysics, CAS Key Laboratory of Infection and Immunity, Chinese Academy of Sciences (CAS) Beijing 100101, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
keywords: Homeobox B7 (HOXB7); bone sialoprotein (BSP); differentiation; mesenchymal stem cells (MSCs); osteogenic