Treatment with an inhibitor of matrix metalloproteinase 9 or cathepsin K lengthens embryonic lower jaw bone.
Treatment with an inhibitor of matrix metalloproteinase 9 or cathepsin K lengthens embryonic lower jaw bone.
复制标题
使用基质金属蛋白酶 9 或组织蛋白酶 K 抑制剂进行治疗可延长胚胎下颌骨。
DOI：
10.1111/ocr.12635
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发表时间：
2023
影响因子：
3.1
通讯作者：
Bumann,ErinE
中科院分区：
文献类型：
--
作者：
Houchen,ClaireJ;Castro,Bethany;HahnLeat,Portia;Mohammad,Nashwa;Hall-Glenn,Faith;Bumann,ErinE
目的骨性错（牙合）畸形是一种常见的错（牙合）畸形，严重的错（牙合）畸形通常采用侵入性手术治疗.最近，颌骨长度已被证明是发育控制破骨细胞。我们的目的是确定抑制破骨细胞分泌的蛋白水解酶对下颌骨长度的鸟类胚胎的抑制基质金属蛋白酶-9（MMP 9）或组织蛋白酶K（CTSK）的影响。方法鹌鹑（Coturnix coturnix japonica）胚胎给予单剂量的MMP 9（iMMP 9）抑制剂，抑制剂CTSK（iCTSK），或车辆在发育阶段时，骨沉积开始发生。在内脏颅大部分钙化的发育阶段，通过微型计算机断层扫描对头部进行扫描，并在3D重建的头骨上放置可再现的标志;使用界标坐标来量化面骨尺寸。结果给予iMMP 9或iCTSK的鹌鹑中约有一半表现出明显的下颌表型，其特征是下颌骨较长，下颌与上颌的比例大于对照胚胎。结论MMP 9和CTSK在破骨细胞介导的下颌骨长度测定中发挥重要作用。MMP 9或CTSK的药理学抑制可能是一种有前途的治疗替代手术治疗骨性颌骨错牙合，但在临床转化之前需要更多的临床前研究。
ObjectivesSkeletal malocclusions are common, and severe malocclusions are treated by invasive surgeries. Recently, jaw bone length has been shown to be developmentally controlled by osteoclasts. Our objective was to determine the effect of inhibiting osteoclast‐secreted proteolytic enzymes on lower jaw bone length of avian embryos by pharmacologically inhibiting matrix metalloproteinase‐9 (MMP9) or cathepsin K (CTSK).MethodsQuail (Coturnix coturnix japonica)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‐computed tomography and reproducible landmarks were placed on 3D‐reconstructed skulls; the landmark coordinates were used to quantify facial bone dimensions.ResultsApproximately 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‐treated embryos exhibited a significant change in midface length and iCTSK‐treated embryos had significant change in nasal bone length.ConclusionMMP9 and CTSK play a role in osteoclast‐mediated 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.