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Recently, jaw bone length has been shown to be developmentally controlled by osteoclasts. Our objective was to determine the effect of inhibiting osteoclast\u2010secreted proteolytic enzymes on lower jaw bone length of avian embryos by pharmacologically inhibiting matrix metalloproteinase\u20109 (MMP9) or cathepsin K (CTSK).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Quail (<jats:italic>Coturnix coturnix japonica)<\/jats:italic> embryos were given a single dose of an inhibitor of MMP9 (iMMP9), an inhibitor CTSK (iCTSK), or vehicle at a developmental stage when bone deposition is beginning to occur. At a developmental stage when the viscerocranium is largely calcified, the heads were scanned via micro\u2010computed tomography and reproducible landmarks were placed on 3D\u2010reconstructed skulls; the landmark coordinates were used to quantify facial bone dimensions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Approximately half of the quail given either iMMP9 or iCTSK demonstrated an overt lower jaw phenotype, characterized by longer lower jaw bones and a greater lower to upper jaw ratio than control embryos. Additionally, iMMP9\u2010treated embryos exhibited a significant change in midface length and iCTSK\u2010treated embryos had significant change in nasal bone length.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MMP9 and CTSK play a role in osteoclast\u2010mediated determination of lower jaw bone length. Pharmacological inhibition of MMP9 or CTSK may be a promising therapeutic alternative to surgery for treating skeletal jaw malocclusions, but more preclinical research is needed prior to clinical translation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ocr.12635","type":"journal-article","created":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T08:04:56Z","timestamp":1674288296000},"page":"500-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Treatment with an inhibitor of matrix metalloproteinase 9 or cathepsin K lengthens embryonic lower jaw bone"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2003-4625","authenticated-orcid":false,"given":"Claire J.","family":"Houchen","sequence":"first","affiliation":[{"name":"Department of Oral and Craniofacial Sciences, School of Dentistry University of Missouri\u2010Kansas City  Kansas City Missouri 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