A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells
A phenylalanine (Phe)-restricted diet is indispensable for individuals suffering from phenylketonuria (PKU). Our previous study reported a low-Phe-containing whey protein hydrolysate (LPH) prepared from a selected whey protein hydrolysate (TA2H). This study aimed to investigate the osteogenic activi...
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MDPI AG
2022-07-01
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| author | Tingting Bu Yuting Ren Songfeng Yu Jiexia Zheng Ling Liu Peilong Sun Jianping Wu Kai Yang |
| author_facet | Tingting Bu Yuting Ren Songfeng Yu Jiexia Zheng Ling Liu Peilong Sun Jianping Wu Kai Yang |
| author_sort | Tingting Bu |
| collection | DOAJ |
| description | A phenylalanine (Phe)-restricted diet is indispensable for individuals suffering from phenylketonuria (PKU). Our previous study reported a low-Phe-containing whey protein hydrolysate (LPH) prepared from a selected whey protein hydrolysate (TA2H). This study aimed to investigate the osteogenic activity of LPH and TA2H in MC3T3-E1 preosteoblast cells and explore the underlying mechanism. Results showed that the treatment of TA2H and LPH (at the final concentrations of 100–1000 μg/mL) had a stimulatory effect on the proliferation, differentiation, and mineralization of MC3T3-E1 cells. The LPH of 1000 μg/mL significantly increased cell proliferation (2.15- ± 0.11-fold) and alkaline phosphatase activity (1.22- ± 0.07-fold), promoted the protein and mRNA levels of runt-related transcription factor 2 (Runx2, 2.50- ± 0.14-fold and 2.97- ± 0.23-fold, respectively), enhanced the expression of differentiation biomarkers (type-I collagen, osteocalcin, and osteopontin), increased calcium deposition (1.56- ± 0.08-fold), and upregulated the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand. The exploration of signaling pathways indicated that the activated p38-dependent Runx2 signaling contributed to the LPH-induced osteogenesis. These results provided evidence, for the first time, that a prepared low-Phe whey protein hydrolysate positively modulated the activity of osteoblasts through the p38/Runx2 pathway, thereby providing a new osteoinductive protein substitute to make functional PKU food. |
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| last_indexed | 2024-03-09T05:07:40Z |
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| series | Nutrients |
| spelling | doaj.art-fed06eed2fd64cd38d6a2c456ae2aa772023-12-03T12:53:45ZengMDPI AGNutrients2072-66432022-07-011415313510.3390/nu14153135A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast CellsTingting Bu0Yuting Ren1Songfeng Yu2Jiexia Zheng3Ling Liu4Peilong Sun5Jianping Wu6Kai Yang7Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, ChinaDepartment of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310027, ChinaCollege of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310027, ChinaCollege of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310027, ChinaDepartment of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, ChinaDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, ChinaA phenylalanine (Phe)-restricted diet is indispensable for individuals suffering from phenylketonuria (PKU). Our previous study reported a low-Phe-containing whey protein hydrolysate (LPH) prepared from a selected whey protein hydrolysate (TA2H). This study aimed to investigate the osteogenic activity of LPH and TA2H in MC3T3-E1 preosteoblast cells and explore the underlying mechanism. Results showed that the treatment of TA2H and LPH (at the final concentrations of 100–1000 μg/mL) had a stimulatory effect on the proliferation, differentiation, and mineralization of MC3T3-E1 cells. The LPH of 1000 μg/mL significantly increased cell proliferation (2.15- ± 0.11-fold) and alkaline phosphatase activity (1.22- ± 0.07-fold), promoted the protein and mRNA levels of runt-related transcription factor 2 (Runx2, 2.50- ± 0.14-fold and 2.97- ± 0.23-fold, respectively), enhanced the expression of differentiation biomarkers (type-I collagen, osteocalcin, and osteopontin), increased calcium deposition (1.56- ± 0.08-fold), and upregulated the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand. The exploration of signaling pathways indicated that the activated p38-dependent Runx2 signaling contributed to the LPH-induced osteogenesis. These results provided evidence, for the first time, that a prepared low-Phe whey protein hydrolysate positively modulated the activity of osteoblasts through the p38/Runx2 pathway, thereby providing a new osteoinductive protein substitute to make functional PKU food.https://www.mdpi.com/2072-6643/14/15/3135phenylketonuriawhey protein hydrolysateosteoblastsdifferentiationrunt-related transcription factor 2p38 mitogen-activated protein kinase |
| spellingShingle | Tingting Bu Yuting Ren Songfeng Yu Jiexia Zheng Ling Liu Peilong Sun Jianping Wu Kai Yang A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells Nutrients phenylketonuria whey protein hydrolysate osteoblasts differentiation runt-related transcription factor 2 p38 mitogen-activated protein kinase |
| title | A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells |
| title_full | A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells |
| title_fullStr | A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells |
| title_full_unstemmed | A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells |
| title_short | A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells |
| title_sort | low phenylalanine containing whey protein hydrolysate stimulates osteogenic activity through the activation of p38 runx2 signaling in osteoblast cells |
| topic | phenylketonuria whey protein hydrolysate osteoblasts differentiation runt-related transcription factor 2 p38 mitogen-activated protein kinase |
| url | https://www.mdpi.com/2072-6643/14/15/3135 |
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