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Open AccessArticle

Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production

1
Department of Natural Sciences, University of Michigan-Dearborn, 4901 Evergreen Rd, Dearborn, MI 48128, USA
2
School of Dentistry, University of Michigan-Ann Arbor, 1011 N University Avenue, Ann Arbor, MI 48103, USA
*
Author to whom correspondence should be addressed.
Academic Editor: David Magne
Int. J. Mol. Sci. 2021, 22(3), 1140; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031140
Received: 8 January 2021 / Revised: 17 January 2021 / Accepted: 20 January 2021 / Published: 24 January 2021
Tissue nonspecific alkaline phosphatase (TNAP/Alpl) 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 Alpl−/− 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. View Full-Text
Keywords: tissue nonspecific alkaline phosphatase; mitochondria; bone marrow stromal cell; bone; muscle; nucleotide adenosine triphosphate tissue nonspecific alkaline phosphatase; mitochondria; bone marrow stromal cell; bone; muscle; nucleotide adenosine triphosphate
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MDPI and ACS Style

Zhang, Z.; Nam, H.K.; Crouch, S.; Hatch, N.E. Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production. Int. J. Mol. Sci. 2021, 22, 1140. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031140

AMA Style

Zhang Z, Nam HK, Crouch S, Hatch NE. Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production. International Journal of Molecular Sciences. 2021; 22(3):1140. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031140

Chicago/Turabian Style

Zhang, Zhi; Nam, Hwa K.; Crouch, Spencer; Hatch, Nan E. 2021. "Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production" Int. J. Mol. Sci. 22, no. 3: 1140. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031140

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