{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:48:11Z","timestamp":1787741291524,"version":"build-2784847793"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1F1A1058657"],"award-info":[{"award-number":["NRF-2021R1F1A1058657"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biomedical Research Institute of Jeonbuk National University Hospital","award":["NRF-2021R1F1A1058657"],"award-info":[{"award-number":["NRF-2021R1F1A1058657"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomimetics"],"abstract":"<jats:p>The effects of aging on the healing capacity of maxillofacial bone defects have not been studied. The aim of this study was to evaluate the effects of aging on the regeneration of round bony defects in the mandible. We created a round-shaped bony defect in the mandibular angle area in rats of different ages (2-[2 M], 10-[10 M], and 20-month-old [20 M]) and evaluated new bone regeneration in these groups. Changes in bone turnover markers such as alkaline phosphatase, procollagen type I N-terminal propeptide (PINP), cross-linked C-telopeptide of type I collagen, and tartrate-resistant acid phosphatase 5B (TRAP5b) were investigated. The bone volume\/total volume and bone mineral density of the 20 M group were significantly higher than those of the 2 M group (p = 0.029, 0.019). A low level of the bone formation marker PINP was observed in the 20 M group, and a high level of the bone resorption marker TRAP5b was observed in the 10 M and 20 M groups. Micro-computed tomography (\u00b5-CT) results showed that older rats had significantly higher bone formation than younger rats, with lower serum levels of PINP and higher levels of TRAP5b. The local environment of the old rat bone defects, surrounded by thickened bone, may have affected the results of our study. In conclusion, old rats showed greater new bone regeneration and healing capacity for round mandibular bone defects. This result was related to the fact that the bone defects in the 20 M rat group provided more favorable conditions for new bone regeneration.<\/jats:p>","DOI":"10.3390\/biomimetics9080466","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:38:20Z","timestamp":1722515900000},"page":"466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of Aging on New Bone Regeneration in a Mandibular Bone Defect in a Rat Model"],"prefix":"10.3390","volume":"9","author":[{"given":"Jung Ho","family":"Park","sequence":"first","affiliation":[{"name":"Department of Orl and Maxillofacial Surgery, School of Dentistry, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Hoon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Orl and Maxillofacial Surgery, School of Dentistry, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwa Young","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School of Dentistry, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5278-3807","authenticated-orcid":false,"given":"Hyun","family":"Seok","sequence":"additional","affiliation":[{"name":"Department of Orl and Maxillofacial Surgery, School of Dentistry, Jeonbuk National University, Jeonju 54896, Republic of Korea"},{"name":"Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Holl\u00fd, D., Klein, M., Mazreku, M., Zamborsk\u00fd, R., Pol\u00e1k, \u0160., Dani\u0161ovi\u010d, \u013d., and Cs\u00f6b\u00f6nyeiov\u00e1, M. (2021). Stem Cells and Their Derivatives\u2014Implications for Alveolar Bone Regeneration: A Comprehensive Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111746"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.orthres.2005.04.003.1100230610","article-title":"Cellular basis for age-related changes in fracture repair","volume":"23","author":"Lu","year":"2005","journal-title":"J. Orthop. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.bone.2010.05.029","article-title":"Influences of age and mechanical stability on volume, microstructure, and mineralization of the fracture callus during bone healing: Is osteoclast activity the key to age-related impaired healing?","volume":"47","author":"Mehta","year":"2010","journal-title":"Bone"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1002\/jor.20124","article-title":"Young, adult, and old rats have similar changes in mRNA expression of many skeletal genes after fracture despite delayed healing with age","volume":"24","author":"Desai","year":"2006","journal-title":"J. Orthop. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ijom.2013.07.742","article-title":"Effect of ageing on healing of bilateral mandibular condyle fractures in a rat model","volume":"43","author":"Tatsumi","year":"2014","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e10068","DOI":"10.1002\/jbm4.10068","article-title":"The effects of age and dose on gene expression and segmental bone defect repair after BMP-2 delivery","volume":"3","author":"Cheng","year":"2019","journal-title":"JBMR Plus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.2106\/00004623-196648060-00018","article-title":"Bone dynamics in metabolic bone disease","volume":"48","author":"Frost","year":"1966","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.exger.2005.11.005","article-title":"Bone and aging: Effects on the maxillofacial skeleton","volume":"41","author":"Kloss","year":"2006","journal-title":"Exp. Gerontol."},{"key":"ref_9","first-page":"2264","article-title":"Changes in quantitative bone histomorphometry in aging healthy men","volume":"81","author":"Clarke","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0736-0266(00)90034-2","article-title":"Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats","volume":"19","author":"Tsahakis","year":"2001","journal-title":"J. Orthop. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/00003086-196300300-00024","article-title":"23 The Periosteum: Autoradiographic Studies on Cellular Proliferation and Transformation Utilizing Tritiated Thymidine","volume":"30","author":"TONNA","year":"1963","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/jbmr.5650110504","article-title":"Age-related changes in osteogenic stem cells in mice","volume":"11","author":"Bergman","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"259","DOI":"10.17305\/bjbms.2013.2337","article-title":"The utility of procollagen type 1 N-terminal propeptide for the bone status assessment in postmenopausal women","volume":"13","author":"Valjevac","year":"2013","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1359\/jbmr.1999.14.7.1203","article-title":"Age-related changes in bone turnover in men","volume":"14","author":"Fatayerji","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0378-5122(96)01042-0","article-title":"Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women","volume":"25","author":"Iki","year":"1996","journal-title":"Maturitas"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.jocd.2013.01.009","article-title":"The effect of age, sex hormones, and bone turnover markers on calcaneal quantitative ultrasonometry in healthy German men","volume":"16","author":"Kyvernitakis","year":"2013","journal-title":"J. Clin. Densitom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9290","DOI":"10.1016\/j.biomaterials.2014.07.051","article-title":"The influence of age on adaptive bone formation and bone resorption","volume":"35","author":"Birkhold","year":"2014","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s001980070116","article-title":"Biochemical measurements of bone turnover in children and adolescents","volume":"11","author":"Szulc","year":"2000","journal-title":"Osteoporos. Int."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shao, J., Zhou, S.-S., Qu, Y., Liang, B.-B., Yu, Q.-H., and Wu, J. (2020). Correlation between bone turnover and metabolic markers with age and gender: A cross-sectional study of hospital information system data. BMC Musculoskelet. Disord., 21.","DOI":"10.1186\/s12891-020-03610-w"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/00001665-200111000-00015","article-title":"Repair of a critical size defect in the rat mandible using allogenic type I collagen","volume":"12","author":"Saadeh","year":"2001","journal-title":"J. Craniofac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, J., Feng, Z., Wei, J., Yu, Y., Luo, J., Zhou, J., Li, Y., Zheng, X., Tang, W., and Liu, L. (2018). Repair of critical-sized mandible defects in aged rat using hypoxia preconditioned BMSCs with up-regulation of Hif-1\u03b1. Int. J. Biol. Sci., 14.","DOI":"10.7150\/ijbs.24158"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: Structure, expression and its function in bone mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1080\/08916930701694667","article-title":"Tartrate-resistant acid phosphatase (TRAP) and the osteoclast\/immune cell dichotomy","volume":"41","author":"Hayman","year":"2008","journal-title":"Autoimmunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s007840100105","article-title":"General and oral aspects of osteoporosis: A review","volume":"5","year":"2001","journal-title":"Clin. Oral Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.actbio.2018.06.035","article-title":"Effect of age on biomaterial-mediated in situ bone tissue regeneration","volume":"78","author":"Liu","year":"2018","journal-title":"Acta. Biomater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1096\/fj.201902779R","article-title":"Differential skeletal response in adult and aged rats to independent and combinatorial stimulation with pulsed electromagnetic fields and mechanical vibration","volume":"34","author":"Cai","year":"2020","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0268-0033(03)00018-4","article-title":"Reduced mechanical load decreases the density, stiffness, and strength of cancellous bone of the mandibular condyle","volume":"18","author":"Giesen","year":"2003","journal-title":"Clin. Biomech."}],"container-title":["Biomimetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2313-7673\/9\/8\/466\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:28:21Z","timestamp":1760110101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2313-7673\/9\/8\/466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,1]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["biomimetics9080466"],"URL":"https:\/\/doi.org\/10.3390\/biomimetics9080466","relation":{},"ISSN":["2313-7673"],"issn-type":[{"value":"2313-7673","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,1]]}}}