MMP-9 deficiency accelerates the progress of periodontitis

MMP-9 deficiency accelerates the progress of periodontitisPeriodontitis is a chronic inflammatory disease caused by periodontopathic bacteria that affects periodontal support tissues. 1 If left untreated, it results in loss of periodontal attachment and alveolar bone resorption.Approximately one-half of adults in the United States older than 30 years have periodontal disease. 2 Though the disease is initiated by bacterial infection, it activates host defense systems that eventually lead to the degradation of the periodontium.During periodontitis, the disease progress involves further production of pro-inflammatory mediators such as cytokines, proteolytic enzymes like matrix metalloproteinases (MMPs), and their inhibitors.MMP-9 is one of the MMPs 1 capable of processing collagen and non-collagen proteins and plays diverse roles in physiological and pathological development.It promotes inflammation in tissues and diseases such as periodontitis.High MMP-9 expression was observed in periodontal diseases.However, several reports demonstrated that MMP-9 is not related to periodontitis. 3 In contrast, MMP-9 mutations in humans are associated with metaphyseal anadysplasia (OMIM 613073) and skeletal defects. 4MMP-9 overexpression attenuates osteoclast (OC) formation and inhibits pro-inflammatory cytokines secretion.MMP-9 knockout (KO) mice develop severe periapical lesions with inflammation. 5This indicates that MMP-9 has dual effects on physiological and pathological development.How MMP-9 regulates alveolar bone metabolism and periodontium during aging has not been described.This study aimed to investigate the effect of MMP-9 on the balance of osteogenesis and osteoclastogenesis in periodontium with aging.We found that MMP-9 KO mice gradually develop deteriorated periodontic tissues with aging.X-ray radiography and micro-computed tomography (mCT) revealed a striking alveolar bone loss in molar mandibular furcation and interdental region of MMP-9 KO mice at 6, 12, and 29 months old compared with controls (Fig. 1AeC).Noticeably, the destruction of alveolar bone in MMP-9 KO mice was more evident with aging.Obvious space in the apical region on the alveolar bone was observed in 12-and 29month-old MMP-9 KO mice.Hyper-mineralized deposits were observed in the alveolar bone of 29-month-old MMP-9 KO mice.Bone mineral density of alveolar bone of 2-, 6-, 12-, and 29-month-old MMP-9 KO mice was also reduced (Fig. 1C).With aging, loss of alveolar bone was gradually prominent in MMP-9 KO.Additionally, molar cusps in MMP-9 KO groups at 6, 12, and 29 months old were worn (Fig. S2).Scanning electron microscopy (SEM) using backscattered electrons also displayed more alveolar bone loss and bone resorption in interdental, furcation, and periapical regions in MMP-9 null mice, especially apical regions of alveolar bone with aging (Fig. S3).To further evaluate the morphological changes in osteocytes and the lacunae-canalicular structures within the alveolar bone, we employed acid-etched SEM.Our examination encompassed 2-, 6-, 12-, and 29-month-old MMP-9 KO mice.SEM images captured at low and middle magnifications (500 mm and 200 mm) revealed evident trabecular bone resorption, with pronounced large lacunae-canalicular structures prominently present in the apical regions of the alveolar bones, particularly in the 6-, 12-, and 29month-old MMP-9 KO mice.Upon closer inspection at high magnification (50 mm), we observed a diminished number of unevenly distributed and irregularly spaced osteocytes in the mutant mice, especially among the aged MMP-9 KO mice.In contrast, osteocytes in the alveolar bones of wildtype mice exhibited a highly organized and evenly dispersed pattern, with distinct outlines.Furthermore, in the 29-month-old MMP-9 KO mice, SEM imaging revealed the deposition of calcium within the trabecular bones (Fig. 1D).These findings suggest that MMP-9 may play a multifaceted role encompassing the regulation of mineralization and the formation and/or maintenance of osteogenesis.The region of interest was evaluated by two-and three-dimensional reconstructions using mCT analysis.Quantitative data analyses revealed bone volume, bone volume/tissue volume, and trabecular thickness in the first molar alveolar bone were significantly low at 6-, 12-and 29-Peer review under responsibility of Chongqing Medical University.

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