Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production
Tissue nonspecific alkaline phosphatase (TNAP/<i>Alpl</i>) is associated with cell stemness; however, the function of TNAP in mesenchymal progenitor cells remains largely unknown. In this study, we aimed to establish an essential role for TNAP in bone and muscle progenitor cells. We inve...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1140 |
| _version_ | 1797407879645364224 |
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| author | Zhi Zhang Hwa Kyung Nam Spencer Crouch Nan E. Hatch |
| author_facet | Zhi Zhang Hwa Kyung Nam Spencer Crouch Nan E. Hatch |
| author_sort | Zhi Zhang |
| collection | DOAJ |
| description | Tissue nonspecific alkaline phosphatase (TNAP/<i>Alpl</i>) is associated with cell stemness; however, the function of TNAP in mesenchymal progenitor cells remains largely unknown. In this study, we aimed to establish an essential role for TNAP in bone and muscle progenitor cells. We investigated the impact of TNAP deficiency on bone formation, mineralization, and differentiation of bone marrow stromal cells. We also pursued studies of proliferation, mitochondrial function and ATP levels in TNAP deficient bone and muscle progenitor cells. We find that TNAP deficiency decreases trabecular bone volume fraction and trabeculation in addition to decreased mineralization. We also find that <i>Alpl</i><sup>−/−</sup> mice (global TNAP knockout mice) exhibit muscle and motor coordination deficiencies similar to those found in individuals with hypophosphatasia (TNAP deficiency). Subsequent studies demonstrate diminished proliferation, with mitochondrial hyperfunction and increased ATP levels in TNAP deficient bone and muscle progenitor cells, plus intracellular expression of TNAP in TNAP+ cranial osteoprogenitors, bone marrow stromal cells, and skeletal muscle progenitor cells. Together, our results indicate that TNAP functions inside bone and muscle progenitor cells to influence mitochondrial respiration and ATP production. Future studies are required to establish mechanisms by which TNAP influences mitochondrial function and determine if modulation of TNAP can alter mitochondrial respiration in vivo. |
| first_indexed | 2024-03-09T03:49:08Z |
| format | Article |
| id | doaj.art-0fdf107ee4e3475eae1f501f3792be64 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:49:08Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0fdf107ee4e3475eae1f501f3792be642023-12-03T14:29:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223114010.3390/ijms22031140Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP ProductionZhi Zhang0Hwa Kyung Nam1Spencer Crouch2Nan E. Hatch3Department of Natural Sciences, University of Michigan-Dearborn, 4901 Evergreen Rd, Dearborn, MI 48128, USASchool of Dentistry, University of Michigan-Ann Arbor, 1011 N University Avenue, Ann Arbor, MI 48103, USASchool of Dentistry, University of Michigan-Ann Arbor, 1011 N University Avenue, Ann Arbor, MI 48103, USASchool of Dentistry, University of Michigan-Ann Arbor, 1011 N University Avenue, Ann Arbor, MI 48103, USATissue nonspecific alkaline phosphatase (TNAP/<i>Alpl</i>) is associated with cell stemness; however, the function of TNAP in mesenchymal progenitor cells remains largely unknown. In this study, we aimed to establish an essential role for TNAP in bone and muscle progenitor cells. We investigated the impact of TNAP deficiency on bone formation, mineralization, and differentiation of bone marrow stromal cells. We also pursued studies of proliferation, mitochondrial function and ATP levels in TNAP deficient bone and muscle progenitor cells. We find that TNAP deficiency decreases trabecular bone volume fraction and trabeculation in addition to decreased mineralization. We also find that <i>Alpl</i><sup>−/−</sup> mice (global TNAP knockout mice) exhibit muscle and motor coordination deficiencies similar to those found in individuals with hypophosphatasia (TNAP deficiency). Subsequent studies demonstrate diminished proliferation, with mitochondrial hyperfunction and increased ATP levels in TNAP deficient bone and muscle progenitor cells, plus intracellular expression of TNAP in TNAP+ cranial osteoprogenitors, bone marrow stromal cells, and skeletal muscle progenitor cells. Together, our results indicate that TNAP functions inside bone and muscle progenitor cells to influence mitochondrial respiration and ATP production. Future studies are required to establish mechanisms by which TNAP influences mitochondrial function and determine if modulation of TNAP can alter mitochondrial respiration in vivo.https://www.mdpi.com/1422-0067/22/3/1140tissue nonspecific alkaline phosphatasemitochondriabone marrow stromal cellbonemusclenucleotide adenosine triphosphate |
| spellingShingle | Zhi Zhang Hwa Kyung Nam Spencer Crouch Nan E. Hatch Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production International Journal of Molecular Sciences tissue nonspecific alkaline phosphatase mitochondria bone marrow stromal cell bone muscle nucleotide adenosine triphosphate |
| title | Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production |
| title_full | Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production |
| title_fullStr | Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production |
| title_full_unstemmed | Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production |
| title_short | Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production |
| title_sort | tissue nonspecific alkaline phosphatase function in bone and muscle progenitor cells control of mitochondrial respiration and atp production |
| topic | tissue nonspecific alkaline phosphatase mitochondria bone marrow stromal cell bone muscle nucleotide adenosine triphosphate |
| url | https://www.mdpi.com/1422-0067/22/3/1140 |
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