{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:50:06Z","timestamp":1790715006714,"version":"4.1.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>The common cellular origin between bone marrow adipocytes (BMAds) and osteoblasts contributes to the intimate link between bone marrow adipose tissue (BMAT) and skeletal health. An imbalance between the differentiation ability of BMSCs towards one of the two lineages occurs in conditions like aging or osteoporosis, where bone mass is decreased. Recently, we showed that the sodium-phosphate co-transporter PiT2\/SLC20A2 is an important determinant for bone mineralization, strength and quality. Since bone mass is reduced in homozygous mutant mice, we investigated in this study whether the BMAT was also affected in <jats:italic>PiT2<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice by assessing the effect of the absence of PiT2 on BMAT volume between 3 and 16 weeks, as well as in an ovariectomy-induced bone loss model. Here we show that the absence of PiT2 in juveniles leads to an increase in the BMAT that does not originate from an increased adipogenic differentiation of bone marrow stromal cells. We show that although <jats:italic>PiT2<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice have higher BMAT volume than control <jats:italic>PiT2<jats:sup>+\/+<\/jats:sup><\/jats:italic> mice at 3 weeks of age, BMAT volume do not increase from 3 to 16 weeks of age, leading to a lower BMAT volume in 16-week-old <jats:italic>PiT2<jats:sup>-\/-<\/jats:sup><\/jats:italic> compared to <jats:italic>PiT2<jats:sup>+\/+<\/jats:sup><\/jats:italic> mice. In contrast, the absence of PiT2 does not prevent the increase in BMAT volume in a model of ovariectomy-induced bone loss. Our data identify <jats:italic>SLC20a2\/PiT2<\/jats:italic> as a novel gene essential for the maintenance of the BMAd pool in adult mice, involving mechanisms of action that remain to be elucidated, but which appear to be independent of the balance between osteoblastic and adipogenic differentiation of BMSCs.<\/jats:p>","DOI":"10.3389\/fendo.2022.921073","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T04:49:28Z","timestamp":1668574168000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["PiT2 deficiency prevents increase of bone marrow adipose tissue during skeletal maturation but not in OVX-induced osteoporosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Giulia","family":"Frangi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Guicheteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Jacquot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Pyka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greet","family":"Kerckhofs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magalie","family":"Feyeux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00eblle","family":"Veziers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Guihard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Halgand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Sourice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Guicheux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Prieur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Beck-Cormier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021119-034513","article-title":"Marrow adipocytes: Origin, structure, and function","volume":"82","author":"de Paula","year":"2020","journal-title":"Annu Rev Physiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.01.008","article-title":"Development, regulation, metabolism and function of bone marrow adipose tissues","volume":"110","author":"Li","year":"2018","journal-title":"Bone"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00138","article-title":"Bone marrow adiposity: Basic and clinical implications","volume":"40","author":"Sebo","year":"2019","journal-title":"Endocr Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.tem.2016.03.016","article-title":"Marrow adipose tissue: Trimming the fat","volume":"27","author":"Scheller","year":"2016","journal-title":"Trends Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00065","article-title":"Reporting guidelines, review of methodological standards, and challenges toward harmonization in bone marrow adiposity research. report of the methodologies working group of the international bone marrow adiposity society","volume":"11","author":"Tratwal","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.01.001","article-title":"Parathyroid hormone directs bone marrow mesenchymal cell fate","volume":"25","author":"Fan","year":"2017","journal-title":"Cell Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.11.034","article-title":"Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia","volume":"53","author":"Iwaniec","year":"2013","journal-title":"Bone"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI92233","article-title":"Ubiquitin ligase RNF146 coordinates bone dynamics and energy metabolism","volume":"127","author":"Matsumoto","year":"2017","journal-title":"J Clin Invest"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93725","article-title":"Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis","volume":"128","author":"Xiao","year":"2018","journal-title":"J Clin Invest"},{"key":"B10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.stem.2018.06.009","article-title":"PGC-1\u03b1 controls skeletal stem cell fate and bone-fat balance in osteoporosis and skeletal aging by inducing TAZ","volume":"23","author":"Yu","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.cmet.2020.09.011","article-title":"Ablation of fat cells in adult mice induces massive bone gain","volume":"32","author":"Zou","year":"2020","journal-title":"Cell Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00141","article-title":"Anatomical variation of age-related changes in vertebral bone marrow composition using chemical shift encoding-based water-fat magnetic resonance imaging","volume":"9","author":"Baum","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1023\/a:1011513223894","article-title":"Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis","volume":"2","author":"Justesen","year":"2001","journal-title":"Biogerontology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2691","article-title":"Reciprocal relation between marrow adiposity and the amount of bone in the axial and appendicular skeleton of young adults","volume":"93","author":"Di Iorgi","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-006-0285-9","article-title":"MRI-Measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women","volume":"18","author":"Shen","year":"2007","journal-title":"Osteoporos Int"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2605","article-title":"Relationship between MRI-measured bone marrow adipose tissue and hip and spine bone mineral density in African-American and Caucasian participants: the CARDIA study","volume":"97","author":"Shen","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1922","article-title":"Bone marrow fat is inversely related to cortical bone in young and old subjects","volume":"96","author":"Wren","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/bonekey.2013.49","article-title":"The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls","volume":"2","author":"Newton","year":"2013","journal-title":"Bonekey Rep"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.23619","article-title":"Bone marrow fat content in the elderly: a reversal of sex difference seen in younger subjects","volume":"36","author":"Griffith","year":"2012","journal-title":"J Magn Reson Imaging"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69209","article-title":"Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells","volume":"10","author":"Aaron","year":"2021","journal-title":"Elife"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3408","article-title":"High-fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice","volume":"33","author":"Tencerova","year":"2018","journal-title":"J Bone Miner Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.053132","article-title":"Identification of a novel function of PiT1 critical for cell proliferation and independent of its phosphate transport activity","volume":"284","author":"Beck","year":"2009","journal-title":"J Biol Chem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009148","article-title":"The phosphate transporter PiT1 (Slc20a1) revealed as a new essential gene for mouse liver development","volume":"5","author":"Beck","year":"2010","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/1747-1028-7-7","article-title":"Regulation of cell proliferation and cell density by the inorganic phosphate transporter PiT1","volume":"7","author":"Byskov","year":"2012","journal-title":"Cell Div"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3609","article-title":"PiT1\/Slc20a1 is required for endoplasmic reticulum homeostasis, chondrocyte survival, and skeletal development","volume":"34","author":"Couasnay","year":"2019","journal-title":"J Bone Miner Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-427302","article-title":"EKLF-driven PIT1 expression is critical for mouse erythroid maturation in vivo and in vitro","volume":"121","author":"Forand","year":"2013","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.yexcr.2014.05.014","article-title":"High levels of the type III inorganic phosphate transporter PiT1 (SLC20A1) can confer faster cell adhesion","volume":"326","author":"Kongsfelt","year":"2014","journal-title":"Exp Cell Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.exphem.2013.01.004","article-title":"Mice lacking the sodium-dependent phosphate import protein, PiT1 (SLC20A1), have a severe defect in terminal erythroid differentiation and early b cell development","volume":"41","author":"Liu","year":"2013","journal-title":"Exp Hematol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"17850","DOI":"10.1038\/s41598-017-17953-3","article-title":"PiT2 regulates neuronal outgrowth through interaction with microtubule-associated protein 1B","volume":"7","author":"Ma","year":"2017","journal-title":"Sci Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.130989","article-title":"Identification of a novel transport-independent function of PiT1\/SLC20A1 in the regulation of TNF-induced apoptosis","volume":"285","author":"Sala\u00fcn","year":"2010","journal-title":"J Biol Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3691","article-title":"Slc20a2, encoding the phosphate transporter PiT2, is an important genetic determinant of bone quality and strength","volume":"34","author":"Beck-Cormier","year":"2019","journal-title":"J Bone Miner Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.071","article-title":"Loss of PiT-2 results in abnormal bone development and decreased bone mineral density and length in mice","volume":"495","author":"Yamada","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2017.12.016","article-title":"Simultaneous three-dimensional visualization of mineralized and soft skeletal tissues by a novel microCT contrast agent with polyoxometalate structure","volume":"159","author":"Kerckhofs","year":"2018","journal-title":"Biomaterials"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00142.2019","article-title":"Ovariectomy increases RANKL protein expression in bone marrow adipocytes of C3H\/HeJ mice","volume":"317","author":"Beekman","year":"2019","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B35","doi-asserted-by":"publisher","first-page":"R100","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"Carpenter","year":"2006","journal-title":"Genome Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/975871","article-title":"Markers for characterization of bone marrow multipotential stromal cells","volume":"2012","author":"Boxall","year":"2012","journal-title":"Stem Cells Int"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051221","article-title":"Differential expression of surface markers in mouse bone marrow mesenchymal stromal cell subpopulations with distinct lineage commitment","volume":"7","author":"Rostovskaya","year":"2012","journal-title":"PloS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.stem.2017.02.009","article-title":"Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration","volume":"20","author":"Ambrosi","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00923","article-title":"Standardised nomenclature, abbreviations, and units for the study of bone marrow adiposity: Report of the nomenclature working group of the international bone marrow adiposity society","volume":"10","author":"Bravenboer","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B41","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1515\/hmbci-2016-0012","article-title":"Bone marrow adipose tissue as an endocrine organ: close to the bone","volume":"28","author":"Sulston","year":"2016","journal-title":"Horm Mol Biol Clin Investig"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1016\/j.cell.2019.04.040","article-title":"A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia","volume":"177","author":"Baryawno","year":"2019","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3313","DOI":"10.1016\/j.celrep.2019.11.004","article-title":"Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging, and inflammation","volume":"29","author":"Helbling","year":"2019","journal-title":"Cell Rep"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0226-8","article-title":"A stromal cell population that inhibits adipogenesis in mammalian fat depots","volume":"559","author":"Schwalie","year":"2018","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1104-8","article-title":"The bone marrow microenvironment at single-cell resolution","volume":"569","author":"Tikhonova","year":"2019","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"7808","DOI":"10.1038\/ncomms8808","article-title":"Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues","volume":"6","author":"Scheller","year":"2015","journal-title":"Nat Commun"},{"key":"B47","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.molmet.2018.02.007","article-title":"Phosphate-dependent FGF23 secretion is modulated by PiT2\/Slc20a2","volume":"11","author":"Bon","year":"2018","journal-title":"Mol Metab"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00188","article-title":"Marrow adipose tissue: Skeletal location, sexual dimorphism, and response to sex steroid deficiency","volume":"8","author":"Lecka-Czernik","year":"2017","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4772","DOI":"10.1038\/s41467-018-06898-4","article-title":"Mettl3-mediated m6A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis","volume":"9","author":"Wu","year":"2018","journal-title":"Nat Commun"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00234.2015","article-title":"Effects of dietary phosphate on glucose and lipid metabolism","volume":"310","author":"Abuduli","year":"2016","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nutd.2015.38","article-title":"Effect of phosphorus supplementation on weight gain and waist circumference of overweight\/obese adults: a randomized clinical trial","volume":"5","author":"Ayoub","year":"2015","journal-title":"Nutr Diabetes"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/nu8120801","article-title":"Phosphorus supplementation recovers the blunted diet-induced thermogenesis of overweight and obese adults: A pilot study","volume":"8","author":"Bassil","year":"2016","journal-title":"Nutrients"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12769","article-title":"Serum phosphate is related to adiposity in healthy adults","volume":"47","author":"Billington","year":"2017","journal-title":"Eur J Clin Invest"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1016\/j.ajpath.2011.01.024","article-title":"A murine model of phosphate nephropathy","volume":"178","author":"Eller","year":"2011","journal-title":"Am J Pathol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.17-141","article-title":"High phosphate diet suppresses lipogenesis in white adipose tissue","volume":"63","author":"Imi","year":"2018","journal-title":"J Clin Biochem Nutr"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12039","article-title":"Low phosphorus status might contribute to the onset of obesity","volume":"14","author":"Obeid","year":"2013","journal-title":"Obes Rev"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2008.08.018","article-title":"Serum phosphate levels and the risk of cardiovascular disease and metabolic syndrome: a double-edged sword","volume":"83","author":"Park","year":"2009","journal-title":"Diabetes Res Clin Pract"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2891","article-title":"Acute phosphate restriction impairs bone formation and increases marrow adipose tissue in growing mice","volume":"31","author":"Ko","year":"2016","journal-title":"J Bone Miner Res"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4312","article-title":"Phosphate restriction impairs mTORC1 signaling leading to increased bone marrow adipose tissue and decreased bone in growing mice","volume":"36","author":"Ko","year":"2021","journal-title":"J Bone Miner Res"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-015-0469-6","article-title":"Slc20a2 is critical for maintaining a physiologic inorganic phosphate level in cerebrospinal fluid","volume":"17","author":"Jensen","year":"2016","journal-title":"Neurogenetics"},{"key":"B61","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.repbio.2015.12.004","article-title":"Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and laminin\u03b11 expressing cells","volume":"16","author":"Wallingford","year":"2016","journal-title":"Reprod Biol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517729811","article-title":"Expression of phosphate transporters during dental mineralization","volume":"97","author":"Merametdjian","year":"2018","journal-title":"J Dent Res"},{"key":"B63","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s12915-020-00880-7","article-title":"PHOSPHO1 is a skeletal regulator of insulin resistance and obesity","volume":"18","author":"Suchacki","year":"2020","journal-title":"BMC Biol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.195","article-title":"Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: a unified model of the mechanisms of initiation of skeletal calcification","volume":"26","author":"Yadav","year":"2011","journal-title":"J Bone Miner Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.921073\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T04:49:32Z","timestamp":1668574172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.921073\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,16]]},"references-count":64,"alternative-id":["10.3389\/fendo.2022.921073"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.921073","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,16]]},"article-number":"921073"}}