{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:01:01Z","timestamp":1774645261755,"version":"3.50.1"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21 HD078864"],"award-info":[{"award-number":["R21 HD078864"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["T90DE021989\u201009"],"award-info":[{"award-number":["T90DE021989\u201009"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2022,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Albright hereditary osteodystrophy (AHO) is caused by heterozygous inactivation of\n GNAS<\/jats:italic>\n , a complex locus that encodes the alpha\u2010stimulatory subunit of heterotrimeric G proteins (Gs\u03b1) in addition to\n NESP55<\/jats:italic>\n and\n XL<\/jats:italic>\n \u03b1\n s<\/jats:italic>\n due to alternative first exons. AHO skeletal manifestations include brachydactyly, brachymetacarpia, compromised adult stature, and subcutaneous ossifications. AHO patients with maternally\u2010inherited\n GNAS<\/jats:italic>\n mutations develop pseudohypoparathyroidism type 1A (PHP1A) with resistance to multiple hormones that mediate their actions through G protein\u2010coupled receptors (GPCRs) requiring Gs\u03b1 (eg, parathyroid hormone [PTH], thyroid\u2010stimulating hormone [TSH], growth hormone\u2013releasing hormone [GHRH], calcitonin) and severe obesity. Paternally\u2010inherited\n GNAS<\/jats:italic>\n mutations cause pseudopseudohypoparathyroidism (PPHP), in which patients have AHO skeletal features but do not develop hormonal resistance or marked obesity. These differences between PHP1A and PPHP are caused by tissue\u2010specific reduction of paternal Gs\u03b1 expression. Previous reports in mice have shown loss of\n Gs\u03b1<\/jats:italic>\n causes osteopenia due to impaired osteoblast number and function and suggest that AHO patients could display evidence of reduced bone mineral density (BMD). However, we previously demonstrated PHP1A patients display normal\u2010increased BMD measurements without any correlation to body mass index or serum PTH. Due to these observed differences between PHP1A and PPHP, we utilized our laboratory's AHO mouse model to address whether\n Gs\u03b1<\/jats:italic>\n heterozygous inactivation differentially affects bone remodeling based on the parental inheritance of the mutation. We identified fundamental distinctions in bone remodeling between mice with paternally\u2010inherited (\n GnasE1+\/\u2212p<\/jats:italic>\n ) versus maternally\u2010inherited (\n GnasE1+\/\u2212m<\/jats:italic>\n ) mutations, and these findings were observed predominantly in female mice. Specifically,\n GnasE1+\/\u2212p<\/jats:italic>\n mice exhibited reduced bone parameters due to impaired bone formation and enhanced bone resorption.\n GnasE1+\/\u2212m<\/jats:italic>\n mice, however, displayed enhanced bone parameters due to both increased osteoblast activity and normal bone resorption. These in vivo distinctions in bone remodeling between\n GnasE1+\/\u2212p<\/jats:italic>\n and\n GnasE1+\/\u2212m<\/jats:italic>\n mice could potentially be related to changes in the bone microenvironment driven by calcitonin\u2010resistance within\n GnasE1+\/\u2212m<\/jats:italic>\n osteoclasts. Further studies are warranted to assess how Gs\u03b1 influences osteoblast\u2013osteoclast coupling. \u00a9 2021 The Authors.\n JBMR Plus<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n <\/jats:p>","DOI":"10.1002\/jbm4.10570","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T18:18:24Z","timestamp":1634753904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Parental Origin of\n \n Gs\u03b1<\/i>\n <\/scp>\n Inactivation Differentially Affects Bone Remodeling in a Mouse Model of Albright Hereditary Osteodystrophy"],"prefix":"10.1093","volume":"6","author":[{"given":"Patrick","family":"McMullan","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Connecticut School of Medicine Farmington CT USA"},{"name":"Department of Reconstructive Sciences University of Connecticut School of Dental Medicine Farmington CT USA"},{"name":"Center for Regenerative Medicine and Skeletal Development University of Connecticut School of Dental Medicine Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Maye","sequence":"additional","affiliation":[{"name":"Department of Reconstructive Sciences University of Connecticut School of Dental Medicine Farmington CT USA"},{"name":"Center for Regenerative Medicine and Skeletal Development University of Connecticut School of Dental Medicine Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingfen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Connecticut School of Medicine Farmington CT USA"},{"name":"Department of Reconstructive Sciences University of Connecticut School of Dental Medicine Farmington CT USA"},{"name":"Center for Regenerative Medicine and Skeletal Development University of Connecticut School of Dental Medicine Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Reconstructive Sciences University of Connecticut School of Dental Medicine Farmington CT USA"},{"name":"Center for Regenerative Medicine and Skeletal Development University of Connecticut School of Dental Medicine Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-610X","authenticated-orcid":false,"given":"Emily L.","family":"Germain\u2010Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Connecticut School of Medicine Farmington CT USA"},{"name":"Department of Reconstructive Sciences University of Connecticut School of Dental Medicine Farmington CT USA"},{"name":"Center for Regenerative Medicine and Skeletal Development University of Connecticut School of Dental Medicine Farmington CT USA"},{"name":"Albright Center, Division of Pediatric Endocrinology Connecticut Children's Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"922","article-title":"Pseudohypoparathyroidism: an example of \u201cSeabright\u2010Bantam syndrome.","volume":"30","author":"Albright F","year":"1942","journal-title":"Endocrinology"},{"key":"e_1_2_8_3_1","first-page":"337","article-title":"Pseudo\u2010pseudohypoparathyroidism","volume":"65","author":"Albright F","year":"1952","journal-title":"Trans Assoc Am Physicians"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0544"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32835a255c"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000783"},{"issue":"2","key":"e_1_2_8_7_1","first-page":"318","article-title":"Short stature, 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