Cellular ATP Synthesis Mediated by Type III Sodium-dependent Phosphate Transporter Pit-1 is Critical to Chondrogenesis

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Nov 16

PMID 21075853

Citations 16

Authors

Atsushi Sugita

Shinji Kawai

Tetsuyuki Hayashibara

Atsuo Amano

Takashi Ooshima

Toshimi Michigami

Hideki Yoshikawa

Toshiyuki Yoneda

Affiliations

Soon will be listed here.

Abstract

Disturbed endochondral ossification in X-linked hypophosphatemia indicates an involvement of P(i) in chondrogenesis. We studied the role of the sodium-dependent P(i) cotransporters (NPT), which are a widely recognized regulator of cellular P(i) homeostasis, and the downstream events in chondrogenesis using Hyp mice, the murine homolog of human X-linked hypophosphatemia. Hyp mice showed reduced apoptosis and mineralization in hypertrophic cartilage. Hyp chondrocytes in culture displayed decreased apoptosis and mineralization compared with WT chondrocytes, whereas glycosaminoglycan synthesis, an early event in chondrogenesis, was not altered. Expression of the type III NPT Pit-1 and P(i) uptake were diminished, and intracellular ATP levels were also reduced in parallel with decreased caspase-9 and caspase-3 activity in Hyp chondrocytes. The competitive NPT inhibitor phosphonoformic acid and ATP synthesis inhibitor 3-bromopyruvate disturbed endochondral ossification with reduced apoptosis in vivo and suppressed apoptosis and mineralization in conjunction with reduced P(i) uptake and ATP synthesis in WT chondrocytes. Overexpression of Pit-1 in Hyp chondrocytes reversed P(i) uptake and ATP synthesis and restored apoptosis and mineralization. Our results suggest that cellular ATP synthesis consequent to P(i) uptake via Pit-1 plays an important role in chondrocyte apoptosis and mineralization, and that chondrogenesis is ATP-dependent.

Citing Articles

Hnrnpk maintains chondrocytes survival and function during growth plate development via regulating Hif1α-glycolysis axis.

Chen Y, Wu J, Zhang S, Gao W, Liao Z, Zhou T Cell Death Dis. 2022; 13(9):803.

PMID: 36127325 PMC: 9489716. DOI: 10.1038/s41419-022-05239-0.

Identification and Characterization of Osmoregulation Related MicroRNAs in Gills of Hybrid Tilapia Under Three Types of Osmotic Stress.

Su H, Fan J, Ma D, Zhu H Front Genet. 2021; 12:526277.

PMID: 33889171 PMC: 8056028. DOI: 10.3389/fgene.2021.526277.

Slc20a1b is essential for hematopoietic stem/progenitor cell expansion in zebrafish.

Chen J, Li G, Lian J, Ma N, Huang Z, Li J Sci China Life Sci. 2021; 64(12):2186-2201.

PMID: 33751369 DOI: 10.1007/s11427-020-1878-8.

Defining the ATPome reveals cross-optimization of metabolic pathways.

Bennett N, Nguyen M, Darch M, Nakaoka H, Cousineau D, Hoeve J Nat Commun. 2020; 11(1):4319.

PMID: 32859923 PMC: 7455733. DOI: 10.1038/s41467-020-18084-6.

An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth.

Uchimura T, Hollander J, Nakamura D, Liu Z, Rosen C, Georgakoudi I Development. 2017; 144(19):3533-3546.

PMID: 28974642 PMC: 5665487. DOI: 10.1242/dev.155598.

References

Yoshiko Y, Candeliere G, Maeda N, Aubin J . Osteoblast autonomous Pi regulation via Pit1 plays a role in bone mineralization. Mol Cell Biol. 2007; 27(12):4465-74. PMC: 1900051. DOI: 10.1128/MCB.00104-07. View

Geschwind J, Ko Y, Torbenson M, Magee C, Pedersen P . Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production. Cancer Res. 2002; 62(14):3909-13. View

Shimomura Y, Yoneda T, Suzuki F . Osteogenesis by chondrocytes from growth cartilage of rat rib. Calcif Tissue Res. 1975; 19(3):179-87. DOI: 10.1007/BF02564002. View

WINTERS R, Graham J, Williams T, McFALLS V, Burnett C . A genetic study of familial hypophosphatemia and vitamin D resistant rickets with a review of the literature. Medicine (Baltimore). 1958; 37(2):97-142. DOI: 10.1097/00005792-195805000-00001. View

Wu L, Guo Y, Genge B, Ishikawa Y, Wuthier R . Transport of inorganic phosphate in primary cultures of chondrocytes isolated from the tibial growth plate of normal adolescent chickens. J Cell Biochem. 2002; 86(3):475-89. DOI: 10.1002/jcb.10240. View

Mansfield K, Teixeira C, Adams C, Shapiro I . Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism. Bone. 2001; 28(1):1-8. DOI: 10.1016/s8756-3282(00)00409-9. View

Jones A, Gillan L, Milmlow D . The anti-glycolytic activity of 3-bromopyruvate on mature boar spermatozoa in vitro. Contraception. 1995; 52(5):317-20. DOI: 10.1016/0010-7824(95)00217-x. View

Zalutskaya A, Cox M, Demay M . Phosphate regulates embryonic endochondral bone development. J Cell Biochem. 2009; 108(3):668-74. PMC: 2972551. DOI: 10.1002/jcb.22302. View

Ko Y, Smith B, Wang Y, Pomper M, Rini D, Torbenson M . Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem Biophys Res Commun. 2004; 324(1):269-75. DOI: 10.1016/j.bbrc.2004.09.047. View

10.

Zuscik M, Hilton M, Zhang X, Chen D, OKeefe R . Regulation of chondrogenesis and chondrocyte differentiation by stress. J Clin Invest. 2008; 118(2):429-38. PMC: 2214711. DOI: 10.1172/JCI34174. View

11.

Wang D, Canaff L, Davidson D, Corluka A, Liu H, Hendy G . Alterations in the sensing and transport of phosphate and calcium by differentiating chondrocytes. J Biol Chem. 2001; 276(36):33995-4005. DOI: 10.1074/jbc.M007757200. View

12.

Magne D, Bluteau G, Faucheux C, Palmer G, Vignes-Colombeix C, Pilet P . Phosphate is a specific signal for ATDC5 chondrocyte maturation and apoptosis-associated mineralization: possible implication of apoptosis in the regulation of endochondral ossification. J Bone Miner Res. 2003; 18(8):1430-42. PMC: 2071932. DOI: 10.1359/jbmr.2003.18.8.1430. View

13.

GIBSON G . Active role of chondrocyte apoptosis in endochondral ossification. Microsc Res Tech. 1998; 43(2):191-204. DOI: 10.1002/(SICI)1097-0029(19981015)43:2<191::AID-JEMT10>3.0.CO;2-T. View

14.

Fukumoto S, Yamashita T . FGF23 is a hormone-regulating phosphate metabolism--unique biological characteristics of FGF23. Bone. 2007; 40(5):1190-5. DOI: 10.1016/j.bone.2006.12.062. View

15.

Miao D, Bai X, Panda D, Karaplis A, Goltzman D, McKee M . Cartilage abnormalities are associated with abnormal Phex expression and with altered matrix protein and MMP-9 localization in Hyp mice. Bone. 2004; 34(4):638-47. DOI: 10.1016/j.bone.2003.12.015. View

16.

Guicheux J, Palmer G, Shukunami C, Hiraki Y, Bonjour J, Caverzasio J . A novel in vitro culture system for analysis of functional role of phosphate transport in endochondral ossification. Bone. 2000; 27(1):69-74. DOI: 10.1016/s8756-3282(00)00302-1. View

17.

Eicher E, SOUTHARD J, Scriver C, Glorieux F . Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. Proc Natl Acad Sci U S A. 1976; 73(12):4667-71. PMC: 431589. DOI: 10.1073/pnas.73.12.4667. View

18.

Boyde A, Shapiro I . Energy dispersive X-ray elemental analysis of isolated epiphyseal growth plate chondrocyte fragments. Histochemistry. 1980; 69(1):85-94. DOI: 10.1007/BF00508369. View

19.

Li P, Nijhawan D, Budihardjo I, Srinivasula S, Ahmad M, Alnemri E . Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997; 91(4):479-89. DOI: 10.1016/s0092-8674(00)80434-1. View

20.

Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K . The Antisenescence Protein Klotho Is Necessary for FGF23-Induced Phosphaturia Klotho Converts Canonical FGF Receptor into a Specific Receptor for FGF23.Nature 444: 770-774, 2006. J Am Soc Nephrol. 2023; 18(3):663-669. DOI: 10.1681/01.asn.0000926868.48235.3d. View