Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production
Abstract
:1. Introduction
2. Results
2.1. TNAP Deficiency Decreases Bone Mineralization and Trabecular Bone Formation by Bone Marrow Stromal Cells
2.2. TNAP Deficiency Increases BMSC Total and Adipocyte Colony Forming Units
2.3. TNAP Deficiency Increases Both Osteoblast and Adipocyte Differentiation of BMSCs
2.4. TNAP Deficiency Decreases Muscle Strength and Impairs Motor Coordination
2.5. TNAP Deficiency Diminishes Progenitor Cell Proliferation and Increases Cell Metabolic Activity
2.6. TNAP Deficiency Alters Mitochondrial Activity and Cell Respiration
2.7. TNAP Deficiency Increases Intracellular ATP Levels in Bone Marrow Stromal and Sol8 Muscle Progenitor Cells
2.8. TNAP is Localized Internally and Co-Localizes with Mitochondria
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Bone Marrow Stromal Cell Isolation
4.3. Collagenous Implant Preparation
4.4. Subcutaneous Implant Placement and Nano Computed Tomography of Ossicles
4.5. Long Bone Micro Computed Tomography
4.6. BMSC Cell Culture and Assay
4.7. BMSC Quantitative Real Time PCR
4.8. Strength and Motor Coordination Tests
4.9. TNAP Deficient Cranial Osteoprogenitor and Muscle Progenitor Cells
4.10. Proliferation and MTT Assays
4.11. Seahorse Agilent Seahorse XF Cell Mito Stress Test
4.12. ATP Measurements
4.13. Immunofluorescent Staining for TNAP and Mitochondria
4.14. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Alpl | Gene encoding Alkaline Phosphatase, Liver/Bone/Kidney |
TNAP | Tissue Nonspecific Alkaline Phosphatase Isozyme |
HPP | Hypophosphatasia |
ATP | Nucleotide Adenosine Triphosphate |
P/S | Penicillin/Streptomycin |
FBS | Fetal Bovine Serum |
AdI/M | Adipocyte induction and maintenance media |
Asc | Ascorbate |
BMSC | Bone marrow stromal cell |
CFU | Colony forming units |
CV | Crystal violet |
OCN | Osteocalcin; bone gamma-carboxyglutamic acid-containing protein (Bglap) |
BSP | Bone Sialoprotein; Integrin Binding Sialoprotein (Ibsp) |
Col1a1 | Collagen, type I, alpha 1 |
OSX | Osterix; Sp family member 7 (Sp7) |
Pparg | Peroxisome proliferator-activated receptor gamma, |
Fabp4 | fatty acid binding protein 4 |
Adipsin | Complement factor D (CFD) |
AdipoQ | Adipocyte specific protein |
GAPDH | Glyceraldehyde 3-phosphate dehydrogenase |
FCCP | Carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone |
OCR | Oxygen consumption rate |
MC3TE1 | Cranial osteoprogenitor cell line |
Sol8 | Skeletal muscle progenitor cell line |
Nano CT | Nano computed tomography |
Micro CT | Micro computed tomography |
References
- Johnson, K.A.; Hessle, L.; Vaingankar, S.; Wennberg, C.; Mauro, S.; Narisawa, S.; Goding, J.W.; Sano, K.; Millan, J.L.; Terkeltaub, R. Osteoblast tissue-nonspecific alkaline phosphatase antagonizes and regulates PC-1. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000, 279, R1365–R1377. [Google Scholar] [CrossRef] [PubMed]
- Fleisch, H.; Straumann, F.; Schenk, R.; Bisaz, S.; Allgower, M. Effect of condensed phosphates on calcification of chick embryo femurs in tissue culture. Am. J. Physiol. 1966, 211, 821–825. [Google Scholar] [CrossRef] [PubMed]
- Hessle, L.; Johnson, K.A.; Anderson, H.C.; Narisawa, S.; Sali, A.; Goding, J.W.; Terkeltaub, R.; Millan, J.L. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc. Natl. Acad. Sci. USA 2002, 99, 9445–9449. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murshed, M.; Harmey, D.; Millan, J.L.; McKee, M.D.; Karsenty, G. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev. 2005, 19, 1093–1104. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mornet, E.; Nunes, M.E. Hypophosphatasia. In Gene Reviews ((R)); Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Stephens, K., Amemiya, A., Eds.; University of Washington: Seattle, WA, USA, 1993. [Google Scholar]
- Fraser, D. Hypophosphatasia. Am. J. Med. 1957, 22, 730–746. [Google Scholar] [CrossRef]
- Whyte, M.P.; Wenkert, D.; Zhang, F. Hypophosphatasia: Natural history study of 101 affected children investigated at one research center. Bone 2016, 93, 125–138. [Google Scholar] [CrossRef]
- Berkseth, K.E.; Tebben, P.J.; Drake, M.T.; Hefferan, T.E.; Jewison, D.E.; Wermers, R.A. Clinical spectrum of hypophosphatasia diagnosed in adults. Bone 2013, 54, 21–27. [Google Scholar] [CrossRef]
- Schmidt, T.; Mussawy, H.; Rolvien, T.; Hawellek, T.; Hubert, J.; Ruther, W.; Amling, M.; Barvencik, F. Clinical, radiographic and biochemical characteristics of adult hypophosphatasia. Osteoporos. Int. 2017, 28, 2653–2662. [Google Scholar] [CrossRef]
- Millan, J.L.; Narisawa, S.; Lemire, I.; Loisel, T.P.; Boileau, G.; Leonard, P.; Gramatikova, S.; Terkeltaub, R.; Camacho, N.P.; McKee, M.D.; et al. Enzyme replacement therapy for murine hypophosphatasia. J. Bone Miner. Res. 2008, 23, 777–787. [Google Scholar] [CrossRef]
- Whyte, M.P.; Greenberg, C.R.; Salman, N.J.; Bober, M.B.; McAlister, W.H.; Wenkert, D.; Van Sickle, B.J.; Simmons, J.H.; Edgar, T.S.; Bauer, M.L.; et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N. Engl. J. Med. 2012, 366, 904–913. [Google Scholar] [CrossRef] [Green Version]
- Whyte, M.P.; Rockman-Greenberg, C.; Ozono, K.; Riese, R.; Moseley, S.; Melian, A.; Thompson, D.D.; Bishop, N.; Hofmann, C. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J. Clin. Endocrinol. Metab. 2016, 101, 334–342. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Whyte, M.P.; Simmons, J.H.; Moseley, S.; Fujita, K.P.; Bishop, N.; Salman, N.J.; Taylor, J.; Phillips, D.; McGinn, M.; McAlister, W.H. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. Lancet Diabetes Endocrinol. 2019, 7, 93–105. [Google Scholar] [CrossRef]
- Whyte, M.P. Hypophosphatasia: Enzyme Replacement Therapy Brings New Opportunities and New Challenges. J. Bone Miner. Res. 2017, 32, 667–675. [Google Scholar] [CrossRef] [Green Version]
- Yasuda, S.Y.; Tsuneyoshi, N.; Sumi, T.; Hasegawa, K.; Tada, T.; Nakatsuji, N.; Suemori, H. NANOG maintains self-renewal of primate ES cells in the absence of a feeder layer. Genes Cells 2006, 11, 1115–1123. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Berstine, E.G.; Hooper, M.L.; Grandchamp, S.; Ephrussi, B. Alkaline phosphatase activity in mouse teratoma. Proc. Natl. Acad. Sci. USA 1973, 70, 3899–3903. [Google Scholar] [CrossRef] [Green Version]
- McElwee, K.J.; Kissling, S.; Wenzel, E.; Huth, A.; Hoffmann, R. Cultured peribulbar dermal sheath cells can induce hair follicle development and contribute to the dermal sheath and dermal papilla. J. Invest. Dermatol. 2003, 121, 1267–1275. [Google Scholar] [CrossRef] [Green Version]
- Esteve, D.; Galitzky, J.; Bouloumie, A.; Fonta, C.; Buchet, R.; Magne, D. Multiple Functions of MSCA-1/TNAP in Adult Mesenchymal Progenitor/Stromal Cells. Stem Cells Int. 2016, 2016, 1815982. [Google Scholar] [CrossRef] [Green Version]
- Kermer, V.; Ritter, M.; Albuquerque, B.; Leib, C.; Stanke, M.; Zimmermann, H. Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation. Neurosci. Lett. 2010, 485, 208–211. [Google Scholar] [CrossRef]
- Sun, J.; Ishii, M.; Ting, M.C.; Maxson, R. Foxc1 controls the growth of the murine frontal bone rudiment by direct regulation of a Bmp response threshold of Msx2. Development 2013, 140, 1034–1044. [Google Scholar] [CrossRef] [Green Version]
- MH, K. The Atlas of Mouse Development; Elsevier Academic Press: Cambridge, MA, USA, 2003. [Google Scholar]
- Gronthos, S.; Fitter, S.; Diamond, P.; Simmons, P.J.; Itescu, S.; Zannettino, A.C. A novel monoclonal antibody (STRO-3) identifies an isoform of tissue nonspecific alkaline phosphatase expressed by multipotent bone marrow stromal stem cells. Stem Cells Dev. 2007, 16, 953–963. [Google Scholar] [CrossRef]
- Liu, W.; Zhang, L.; Xuan, K.; Hu, C.; Liu, S.; Liao, L.; Li, B.; Jin, F.; Shi, S.; Jin, Y. Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells. Bone Res. 2018, 6, 27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nam, H.K.; Vesela, I.; Siismets, E.; Hatch, N.E. Tissue nonspecific alkaline phosphatase promotes calvarial progenitor cell cycle progression and cytokinesis via Erk1,2. Bone 2019, 120, 125–136. [Google Scholar] [CrossRef] [PubMed]
- Bhatti, J.S.; Bhatti, G.K.; Reddy, P.H. Mitochondrial dysfunction and oxidative stress in metabolic disorders—A step towards mitochondria based therapeutic strategies. Biochim. Biophys. Acta Mol. Basis Dis. 2017, 1863, 1066–1077. [Google Scholar] [CrossRef] [PubMed]
- Krishnamurthy, V.R.; Baird, B.C.; Wei, G.; Greene, T.; Raphael, K.; Beddhu, S. Associations of serum alkaline phosphatase with metabolic syndrome and mortality. Am. J. Med. 2011, 124, 566.e1–566.e7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Williams, D.K.; Pinzon, C.; Huggins, S.; Pryor, J.H.; Falck, A.; Herman, F.; Oldeschulte, J.; Chavez, M.B.; Foster, B.L.; White, S.H.; et al. Genetic engineering a large animal model of human hypophosphatasia in sheep. Sci. Rep. 2018, 8, 16945. [Google Scholar] [CrossRef]
- Kishnani, P.S.; Rockman-Greenberg, C.; Rauch, F.; Bhatti, M.T.; Moseley, S.; Denker, A.E.; Watsky, E.; Whyte, M.P. Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone 2019, 121, 149–162. [Google Scholar] [CrossRef]
- Anderson, H.C.; Harmey, D.; Camacho, N.P.; Garimella, R.; Sipe, J.B.; Tague, S.; Bi, X.; Johnson, K.; Terkeltaub, R.; Millan, J.L. Sustained osteomalacia of long bones despite major improvement in other hypophosphatasia-related mineral deficits in tissue nonspecific alkaline phosphatase/nucleotide pyrophosphatase phosphodiesterase 1 double-deficient mice. Am. J. Pathol. 2005, 166, 1711–1720. [Google Scholar] [CrossRef] [Green Version]
- Ponce, M.L.; Koelling, S.; Kluever, A.; Heinemann, D.E.; Miosge, N.; Wulf, G.; Frosch, K.H.; Schutze, N.; Hufner, M.; Siggelkow, H. Coexpression of osteogenic and adipogenic differentiation markers in selected subpopulations of primary human mesenchymal progenitor cells. J. Cell. Biochem. 2008, 104, 1342–1355. [Google Scholar] [CrossRef]
- Wennberg, C.; Hessle, L.; Lundberg, P.; Mauro, S.; Narisawa, S.; Lerner, U.H.; Millan, J.L. Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice. J. Bone Miner. Res. 2000, 15, 1879–1888. [Google Scholar] [CrossRef]
- Villa-Bellosta, R.; Rivera-Torres, J.; Osorio, F.G.; Acin-Perez, R.; Enriquez, J.A.; Lopez-Otin, C.; Andres, V. Defective extracellular pyrophosphate metabolism promotes vascular calcification in a mouse model of Hutchinson-Gilford progeria syndrome that is ameliorated on pyrophosphate treatment. Circulation 2013, 127, 2442–2451. [Google Scholar] [CrossRef] [Green Version]
- Wang, D.; Liu, Y.; Zhang, R.; Zhang, F.; Sui, W.; Chen, L.; Zheng, R.; Chen, X.; Wen, F.; Ouyang, H.W.; et al. Apoptotic transition of senescent cells accompanied with mitochondrial hyper-function. Oncotarget 2016, 7, 28286–28300. [Google Scholar] [CrossRef] [PubMed]
- Shares, B.H.; Busch, M.; White, N.; Shum, L.; Eliseev, R.A. Active mitochondria support osteogenic differentiation by stimulating beta-catenin acetylation. J. Biol. Chem. 2018, 293, 16019–16027. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Romanello, V.; Sandri, M. Mitochondrial Quality Control and Muscle Mass Maintenance. Front. Physiol. 2015, 6, 422. [Google Scholar] [CrossRef] [PubMed]
- Kramer, P.A.; Duan, J.; Qian, W.J.; Marcinek, D.J. The Measurement of Reversible Redox Dependent Post-translational Modifications and Their Regulation of Mitochondrial and Skeletal Muscle Function. Front. Physiol. 2015, 6, 347. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lopez-Crisosto, C.; Pennanen, C.; Vasquez-Trincado, C.; Morales, P.E.; Bravo-Sagua, R.; Quest, A.F.G.; Chiong, M.; Lavandero, S. Sarcoplasmic reticulum-mitochondria communication in cardiovascular pathophysiology. Nat. Rev. Cardiol. 2017, 14, 342–360. [Google Scholar] [CrossRef] [PubMed]
- Kjobsted, R.; Hingst, J.R.; Fentz, J.; Foretz, M.; Sanz, M.N.; Pehmoller, C.; Shum, M.; Marette, A.; Mounier, R.; Treebak, J.T.; et al. AMPK in skeletal muscle function and metabolism. FASEB J. 2018, 32, 1741–1777. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohlebusch, B.; Borst, A.; Frankenbach, T.; Klopocki, E.; Jakob, F.; Liedtke, D.; Graser, S. Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development. Sci. Rep. 2020, 10, 13321. [Google Scholar] [CrossRef]
- Liedtke, D.; Hofmann, C.; Jakob, F.; Klopocki, E.; Graser, S. Tissue-Nonspecific Alkaline Phosphatase-A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease. Biomolecules 2020, 10, 1648. [Google Scholar] [CrossRef]
- Sebastian-Serrano, A.; de Diego-Garcia, L.; Martinez-Frailes, C.; Avila, J.; Zimmermann, H.; Millan, J.L.; Miras-Portugal, M.T.; Diaz-Hernandez, M. Tissue-nonspecific Alkaline Phosphatase Regulates Purinergic Transmission in the Central Nervous System During Development and Disease. Comput. Struct. Biotechnol. J. 2015, 13, 95–100. [Google Scholar] [CrossRef] [Green Version]
- Cheung, K.K.; Chan, W.Y.; Burnstock, G. Expression of P2X purinoceptors during rat brain development and their inhibitory role on motor axon outgrowth in neural tube explant cultures. Neuroscience 2005, 133, 937–945. [Google Scholar] [CrossRef]
- Ziganshin, A.U.; Khairullin, A.E.; Hoyle, C.H.V.; Grishin, S.N. Modulatory Roles of ATP and Adenosine in Cholinergic Neuromuscular Transmission. Int. J. Mol. Sci. 2020, 21, 6423. [Google Scholar] [CrossRef] [PubMed]
- Hanics, J.; Barna, J.; Xiao, J.; Millan, J.L.; Fonta, C.; Negyessy, L. Ablation of TNAP function compromises myelination and synaptogenesis in the mouse brain. Cell Tissue Res. 2012, 349, 459–471. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Langer, D.; Ikehara, Y.; Takebayashi, H.; Hawkes, R.; Zimmermann, H. The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones. Neuroscience 2007, 150, 863–879. [Google Scholar] [CrossRef] [PubMed]
- Wirths, S.; Malenke, E.; Kluba, T.; Rieger, S.; Muller, M.R.; Schleicher, S.; Hann von Weyhern, C.; Nagl, F.; Fend, F.; Vogel, W.; et al. Shared cell surface marker expression in mesenchymal stem cells and adult sarcomas. Stem Cells Transl. Med. 2013, 2, 53–60. [Google Scholar] [CrossRef]
- Kim, Y.H.; Yoon, D.S.; Kim, H.O.; Lee, J.W. Characterization of different subpopulations from bone marrow-derived mesenchymal stromal cells by alkaline phosphatase expression. Stem Cells Dev. 2012, 21, 2958–2968. [Google Scholar] [CrossRef] [Green Version]
- Liu, W.; Zhang, L.; Xuan, K.; Hu, C.; Li, L.; Zhang, Y.; Jin, F.; Jin, Y. Alkaline Phosphatase Controls Lineage Switching of Mesenchymal Stem Cells by Regulating the LRP6/GSK3beta Complex in Hypophosphatasia. Theranostics 2018, 8, 5575–5592. [Google Scholar] [CrossRef]
- Shibayama, J.; Taylor, T.G.; Venable, P.W.; Rhodes, N.L.; Gil, R.B.; Warren, M.; Wende, A.R.; Abel, E.D.; Cox, J.; Spitzer, K.W.; et al. Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: Evidence for the protective role of inorganic pyrophosphate. PLoS ONE 2013, 8, e57821. [Google Scholar] [CrossRef] [Green Version]
- Galloway, C.A.; Yoon, Y. Mitochondrial morphology in metabolic diseases. Antioxid Redox Signal. 2013, 19, 415–430. [Google Scholar] [CrossRef] [Green Version]
- Nisoli, E.; Clementi, E.; Carruba, M.O.; Moncada, S. Defective mitochondrial biogenesis: A hallmark of the high cardiovascular risk in the metabolic syndrome? Circ. Res. 2007, 100, 795–806. [Google Scholar] [CrossRef] [Green Version]
- Luzzo, K.M.; Wang, Q.; Purcell, S.H.; Chi, M.; Jimenez, P.T.; Grindler, N.; Schedl, T.; Moley, K.H. High fat diet induced developmental defects in the mouse: Oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS ONE 2012, 7, e49217. [Google Scholar] [CrossRef] [Green Version]
- Saben, J.L.; Boudoures, A.L.; Asghar, Z.; Thompson, A.; Drury, A.; Zhang, W.; Chi, M.; Cusumano, A.; Scheaffer, S.; Moley, K.H. Maternal Metabolic Syndrome Programs Mitochondrial Dysfunction via Germline Changes across Three Generations. Cell Rep. 2016, 16, 1–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shi, Y.; Saben, J.L.; He, G.; Moley, K.H.; Long, F. Diet-Induced Metabolic Dysregulation in Female Mice Causes Osteopenia in Adult Offspring. J. Endocr. Soc. 2020, 4, bvaa028. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Waymire, K.G.; Mahuren, J.D.; Jaje, J.M.; Guilarte, T.R.; Coburn, S.P.; MacGregor, G.R. Mice lacking tissue non–specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B–6. Nat. Genet. 1995, 11, 45–51. [Google Scholar] [CrossRef] [PubMed]
- Narisawa, S.; Fröhlander, N.; Millán, J.L. Inactivation of two mouse alkaline phosphatase genes and establishment of a model of infantile hypophosphatasia. Dev. Dyn. 1997, 208, 432–446. [Google Scholar] [CrossRef]
- Liu, J.; Nam, H.K.; Campbell, C.; Gasque, K.C.; Millan, J.L.; Hatch, N.E. Tissue-nonspecific alkaline phosphatase deficiency causes abnormal craniofacial bone development in the Alpl(-/-) mouse model of infantile hypophosphatasia. Bone 2014, 67, 81–94. [Google Scholar] [CrossRef] [Green Version]
- Liu, J.; Nam, H.K.; Wang, E.; Hatch, N.E. Further analysis of the Crouzon mouse: Effects of the FGFR2(C342Y) mutation are cranial bone-dependent. Calcif. Tissue Int. 2013, 92, 451–466. [Google Scholar] [CrossRef] [Green Version]
- Yagiela, J.A.; Woodbury, D.M. Enzymatic isolation of osteoblasts from fetal rat calvaria. Anat. Rec. 1977, 188, 287–306. [Google Scholar] [CrossRef]
- Bellows, C.G.; Aubin, J.E.; Heersche, J.N.; Antosz, M.E. Mineralized bone nodules formed in vitro from enzymatically released rat calvaria cell populations. Calcif. Tissue Int. 1986, 38, 143–154. [Google Scholar] [CrossRef]
Cell Type | Geno Type | Basal Respiration | ATP Production | Proton Leak | Maximal Respiration | Space Capacity | Non-Mito Oxygen Consumption |
---|---|---|---|---|---|---|---|
MC3T3E1 Cranial Osteoprogenitor Cell Line | NT shRNA | 2.4±0.3 | 1.9±0.3 | 0.54±0.08 | 6.0±1.2 | 3.6±0.90 | 0.9±0.4 |
Alpl shRNA | 4.8±0.6 ** | 3.8±0.6 * | 0.99±0.03 ** | 11.5±2.2 * | 6.7±1.7 | 1.6±0.5 | |
Primary Cranial Osteoprogenitor Cells | Alpl+/+ | 10.8±0.6 | 9.3±0.5 | 1.40±0.20 | 28.8±5.5 | 18.0±5.5 | 4.9±0.5 |
Alpl−/− | 12.6±1.0 ** | 10.3±0.5 * | 2.27±0.56 * | 33.6±5.9 | 21.0±6.1 | 6.3±0.6 ** | |
Primary Bone Marrow Stromal Cells | Alpl+/+ | 6.2±0.3 | 5.2±0.4 | 1.05±0.48 | 12.0±1.7 | 5.8±1.6 | 3.0±0.9 |
Alpl−/− | 9.4±0.8 * | 7.5±0.7 ** | 1.83±0.33 | 16.4±1.2 * | 7.1±1.6 | 2.1±0.4 | |
Sol8 Skeletal Muscle Cell Line | NT shRNA | 33.9±4.6 | 27.1±3.7 | 6.83±1.63 | 72.1±13.5 | 38.2±10.0 | 11.9±4.3 |
Alpl shRNA | 50.7±6.3 ** | 40.6±.8 ** | 10.14±1.58 ** | 152.5±21.2 *** | 101.8±16.9 *** | 18.4±2.7 * |
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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://doi.org/10.3390/ijms22031140
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://doi.org/10.3390/ijms22031140
Chicago/Turabian StyleZhang, Zhi, Hwa Kyung Nam, Spencer Crouch, and Nan E. Hatch. 2021. "Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production" International Journal of Molecular Sciences 22, no. 3: 1140. https://doi.org/10.3390/ijms22031140