{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:03:47Z","timestamp":1791644627664,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31971247"],"award-info":[{"award-number":["31971247"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801018"],"award-info":[{"award-number":["81801018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to evaluate the effects of local application of parathyroid hormone (PTH) or parathyroid hormone\u2010related protein (PTHrP) on osteogenesis and osteoclastogenesis during orthodontic tooth movement (OTM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>Periodontal bone remodeling is the crucial biological process in the OTM that involves both bone resorption and formation, with the former more important as the initiator. PTH or PTHrP both play dual roles in bone remodeling regulation, and the balance may shift to the bone resorption side when they are given continuously, suggesting them as potential candidate medicine for OTM acceleration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 40 rats underwent orthodontic mesialization of the maxillary first molars and received no micro\u2010perforation (MOP), or MOP followed by injection of temperature\u2010sensitive hydrogel containing PTH, PTHrP, or normal saline. The rats were sacrificed after 2\u2010week OTM, except for the relapse groups, which had one more week of observation after removal of the force appliances. The amount of tooth movement, rate of relapse after OTM, and effects on the bone remodeling were assessed through micro\u2010computed tomography (\u03bcCT) analysis, alkaline phosphatase (ALP) assay, alizarin red staining, tartrate\u2010resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) analysis, Western blot (WB), and quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR). The effects of PTHrP on the osteogenic differentiation of human periodontal ligament cells (hPDLCs) were explored <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cumulative release of PTH or PTHrP from PECE hydrogels was beyond 75% at 14\u00a0days in a sustained manner. After the intervention <jats:italic>in vivo<\/jats:italic>, the distance of OTM in the PTH (0.78\u00a0\u00b1\u00a00.06\u00a0mm) or PTHrP (0.81\u00a0\u00b1\u00a00.04\u00a0mm) group was significantly larger than that of the MOP only (0.51\u00a0\u00b1\u00a00.04\u00a0mm) or the no MOP (0.46\u00a0\u00b1\u00a00.05\u00a0mm) group. Moreover, PTH injection significantly reduced the rate of relapse after OTM (25.7\u00a0\u00b1\u00a04.3%) compared to the control (69.6\u00a0\u00b1\u00a06.1%). \u03bcCT analysis showed decreased BV\/TV, BS\/BV, and Tb.N, while increased Tb.Sp of alveolar bone in the PTH or PTHrP group. There were also more TRAP\u2010positive osteoclasts in the PTH or PTHrP group with a significantly enhanced ratio of receptor activator of nuclear factor\u2010\u03baB ligand (RANKL)\/osteoprotegerin (OPG). The protein expressions of PTH\/PTHrP type 1 receptor (PTHR1), alkaline phosphatase (ALP), osteocalcin (OCN), runt\u2010related transcription factor 2 (RUNX2), and \u03b2\u2010catenin were significantly increased in the PTH or PTHrP group, as well as the gene expressions of <jats:italic>Pth1r<\/jats:italic>, <jats:italic>Bglap<\/jats:italic>, and <jats:italic>Alpl<\/jats:italic>. There was no significant difference between the effects of PTH and PTHrP. Nevertheless, inhibition of PTHrP on the osteogenic differentiation of hPDLCs was detected <jats:italic>in vitro<\/jats:italic> with decreased expression of OCN, RUNX2, COL\u20101, and ALP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Local injection of either PTH or PTHrP carried by controlled release PECE hydrogel similarly enhances OTM in rats through regulating periodontal bone remodeling, which deserves further study for potential clinical application.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12885","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T07:33:40Z","timestamp":1618558420000},"page":"885-896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["PTH\/PTHrP in controlled release hydrogel enhances orthodontic tooth movement by regulating periodontal bone 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