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- Title
Role of PCSK9 in the Development of Mouse Periodontitis Before and After Treatment: A Double-Edged Sword.
- Authors
Hua Ling Sun; Yan Ru Wu; Fang Fang Song; Jing Gan; Li Yuan Huang; Lu Zhang; Cui Huang; Sun, Hua Ling; Wu, Yan Ru; Song, Fang Fang; Gan, Jing; Huang, Li Yuan; Zhang, Lu; Huang, Cui
- Abstract
Periodontitis is a highly prevalent infectious disease associated genetically with coronary heart disease (CHD). The effects of proprotein convertase subtilisin/kexin type 9 (PCSK9), a critical regulator of CHD, on periodontitis have not been studied to date. Here, we found that PCSK9 expression was increased in periodontitis patients and Porphyromonas gingivalis (Pg)-infected mice. Loss of PCSK9 attenuated Pg-induced periodontal bone loss in mice. First, PCSK9 deficiency reduced the release of inflammation-associated cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin 1β, in vitro and in vivo. Second, its deficiency enhanced Pg and endotoxin clearance during Pg invasion in part by upregulating CD36 and low-density lipoprotein receptor (LDLR), respectively. However, after berberine treatment, periodontal bone regeneration in the PCSK9 knockout group was significantly lower than that in wild-type. This was because PCSK9 overexpression promoted osteogenic differentiation of periodontal ligament stem cells (PDLCs) prechallenged by TNF-α. Furthermore, PCSK9 could rescue PDLC osteogenesis by repressing the NF-κB signaling pathway by interacting with TRAF2. These results suggest that PCSK9 may be a potent drug target for treating periodontitis.
- Subjects
PROPROTEIN convertases; PERIODONTITIS; CORONARY disease; RISK factors of periodontal disease; MICROBIAL invasiveness
- Publication
Journal of Infectious Diseases, 2018, Vol 217, Issue 4, p667
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jix574