KR12a6 promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells via BMP/SMAD signaling.
Mol Med Rep
; 21(1): 61-68, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31939626
ABSTRACT
Considering the increased resistance to antibiotics in the clinic and the ideal antibacterial properties of KR12, the effects of KR12a6, an important analogue of KR12, on the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. Osteogenic differentiationassociated experiments were conducted in hBMSCs, and KR12a6 was used as an additional stimulating factor during osteogenic induction. Quantitative analysis of alkaline phosphatase (ALP) and alizarin red staining, and reverse transcriptionquantitative PCR analysis of the expression of osteogenesisassociated genes were performed to determine the effects of KR12a6 on the osteogenic differentiation of hBMSCs. LDN212854 was selected to selectively suppress BMP/SMAD signaling. Western blotting was performed to investigate the underlying mechanisms. The intensity of ALP and alizarin red staining gradually increased with increasing KR12a6 concentrations. KR12a6 induced the strongest staining at 40 µg/ml, whereas 60 µg/ml and 80 µg/ml concentrations did not further increase the intensity of staining. The mRNA expression levels of RUNX2 and ALP increased in a dosedependent manner as early as 3 days postKR12a6 treatment. The mRNA expression of COL1A1, BSP and BMP2 exhibited significant upregulation from day 7 postKR12a6 treatment. In contrast, the mRNA levels of OSX, OCN and OPN were enhanced dramatically at day 14 following KR12a6 stimulation. Additionally, KR12a6 significantly promoted the phosphorylation of Smad1/5. Furthermore, LDN212854 suppressed the activation of Smad1/5 and inhibited the upregulation of several osteogenic differentiationassociated genes in KR12a6treated hBMSCs. KR12a6 promoted the osteogenic differentiation of hBMSCs via BMP/SMAD signaling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Osteogénesis
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Proteína Smad1
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Proteína Smad5
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Proteína Morfogenética Ósea 2
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Imidazoles
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Nylons
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Med Rep
Año:
2020
Tipo del documento:
Article