Molecular insights into an ancient form of Paget's disease of bone

Shaw, Barry; Burrell, Carla L.; Green, Darrell; Navarro-Martinez, Ana; Scott, Daniel; Daroszewska, Anna; van't Hof, Rob; Smith, Lynn; Hargrave, Frank; Mistry, Sharad; Bottrill, Andrew; Kessler, Benedikt; Fisher, Roman; Singh, Archana; Dalmay, Tamas; Fraser, William D.; Henneberger, Kirstin; King, Turi; Gonzalez, Silvia; Layfield, Robert

Abstract

We identify an ancient and atypical form of Paget’s disease of bone (PDB) in a collection of medieval skeletons exhibiting unusually extensive pathological changes, high disease prevalence, and low age-at-death estimations. Proteomic analysis of ancient bone-preserved proteins combined with analysis of small RNAs supports a retrospective diagnosis of PDB. Remains affected by other skeletal disorders may therefore hold a chemical memory amenable to similar molecular interrogation. Abnormalities in a contemporary PDB-linked protein detected in ancient tooth samples indicate that dentition may represent an unexplored storehouse for the study of skeletal disorders. Our work provides insights into the natural history of PDB and prompts a similar revaluation of other archaeological collections.

Citation

Shaw, B., Burrell, C. L., Green, D., Navarro-Martinez, A., Scott, D., Daroszewska, A., …Layfield, R. (2019). Molecular insights into an ancient form of Paget's disease of bone. Proceedings of the National Academy of Sciences, 116(21), 10463-10472. https://doi.org/10.1073/pnas.1820556116

• Journal Article Type: Article
• Acceptance Date: Mar 26, 2019
• Online Publication Date: Apr 29, 2019
• Publication Date: Apr 29, 2019
• Deposit Date: Apr 29, 2019
• Publicly Available Date: Oct 30, 2019
• Journal: Proceedings of the National Academy of Sciences
• Print ISSN: 0027-8424
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 116
• Issue: 21
• Pages: 10463-10472
• DOI: https://doi.org/10.1073/pnas.1820556116
• Public URL: https://nottingham-repository.worktribe.com/output/1851053
• Publisher URL: https://www.pnas.org/content/early/2019/04/24/1820556116
• Contract Date: Apr 29, 2019