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Although living dinosaurs (i.e., extant birds) exhibit a sex\u2010specific tissue called medullary bone that is unique to females, the confident identification of this tissue in non\u2010avian archosaurs has proven a challenge. Tracing the evolution of medullary bone is complicated by existing variation of medullary bone tissues in living species; hypotheses that medullary bone structure or chemistry varied during its evolution; and a lack of studies aimed at distinguishing medullary bone from other types of endosteal tissues with which it shares microstructural and developmental characteristics, such as pathological tissues. A recent study attempted to capitalize on the molecular signature of medullary bone, which, in living birds, contains specific markers such as the sulfated glycosaminoglycan keratan sulfate, to support the proposed identification of medullary bone of a non\u2010avian dinosaur specimen (<jats:italic>Tyrannosaurus rex<\/jats:italic> MOR 1125). Purported medullary bone samples of MOR 1125 reacted positively to histochemical analyses and the single pathological control tested (avian osteopetrosis) did not, suggesting the presence of keratan sulfate might serve to definitively discriminate these tissues for future studies. To further test these results, we sampled 20 avian bone pathologies of various etiologies (18 species), and several MB samples. Our new data universally support keratan sulfate as a reliable marker of medullary bone in birds. However, we also find that reactivity varies among pathological bone tissues, with reactivity in some pathologies indistinguishable from MB. In the current sample, some pathologies comprised of chondroid bone (often a major constituent of skeletal pathologies and developing fracture calluses in vertebrates) contain keratan sulfate. We note that beyond chemistry, chondroid bone shares many characteristics with medullary bone (fibrous matrix, numerous and large cell lacunae, potential endosteal origin, trabecular architecture) and medullary bone has even been considered by some to be a type of chondroid bone. Our results suggest that the presence of keratan sulfate is not exclusive evidence for MB, but rather must be used as one in a suite of criteria available for identifying medullary bone (and thus gravid females) in non\u2010avian dinosaur specimens. Future studies should investigate whether there are definite chemical or microstructural differences between medullary bone and reactive chondroid bone that can discriminate these tissues.<\/jats:p>","DOI":"10.1111\/joa.13388","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T02:01:20Z","timestamp":1609812080000},"page":"1296-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Keratan sulfate as a marker for medullary bone in fossil vertebrates"],"prefix":"10.1111","volume":"238","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9798-176X","authenticated-orcid":false,"given":"Aurore","family":"Canoville","sequence":"first","affiliation":[{"name":"Paleontology North Carolina Museum of Natural Sciences Raleigh NC USA"},{"name":"Department of Biological Sciences North Carolina State University Raleigh NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-1990","authenticated-orcid":false,"given":"Lindsay E.","family":"Zanno","sequence":"additional","affiliation":[{"name":"Paleontology North Carolina Museum of Natural Sciences Raleigh NC USA"},{"name":"Department of Biological Sciences North Carolina State University Raleigh NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1122-9826","authenticated-orcid":false,"given":"Wenxia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences North Carolina State University Raleigh NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0427-3829","authenticated-orcid":false,"given":"Mary H.","family":"Schweitzer","sequence":"additional","affiliation":[{"name":"Paleontology North Carolina Museum of Natural Sciences Raleigh NC USA"},{"name":"Department of Biological Sciences North Carolina State University Raleigh NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crpv.2014.12.004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09259-x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwz206"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.16.3.876-884.1977"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/02724634.2011.557112"},{"key":"e_1_2_8_7_1","volume-title":"Chondroid bone, secondary cartilage and metaplasia","author":"Beresford W.A.","year":"1981"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00218592"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0305-0491(71)90084-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12862-019-1402-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2019.0133"},{"key":"e_1_2_8_12_1","unstructured":"Canoville A. Zanno L.E. Zheng W.&Schweitzer M.H.(2020b)Keratan sulfate as a marker for medullary bone in fossil vertebrates. MorphoSource repository project no. P1053. 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