# The Alterations in CD14 Expression in Periodontitis:
## 1 Introduction  
Periodontitis is a multifactorial, inflammatory disease that causes the destruction of the periodontal tissues and, as the ultimate endpoint, can even lead to the loss of the tooth [1]. According to a recent study by [PERSON], et al. [2], the global burden of periodontal diseases remains high, with the most severe form affecting 11.2% of the world's population [3]. _Porphyomonas gingivalis_, a gram-negative bacterium, is currently considered a keystone pathogen [4] and shows a strong association with periodontitis [5]. Recent studies have underscored that the pathogenicity of _P. gingivalis_ lies in its constituents: Lipopolysaccharideaccharide (LPS), gingipains, and fimbraise/pili [6]. Each factor has been widely studied, and integral roles in the progression of periodontitis have been elucidated [6]. The human innate immune system comprises a family of pattern recognition receptors, termed toll-like receptors (TLRSs), which recognize various bacterial components and initiate the inflammatory reaction in response [7]. The recognition of bacterial components by TLRs is facilitated by numerous co-receptors, with the cluster of differentiation (CD) 14 being one of them [8].  
Originally described as a myeloid differentiation antigen detected on mature monocytes/macrophages [9] and neutrophils, the CD14 molecule is a key factor for the innate recognition of bacteria [9, 10]. CD14, a 55-kDa glycoprotein, exists in two forms, a solubleform (sCD14) [11] and a membrane bound form (mCD14) [11]. The membrane bound form is found mainly on mature monocytes, macrophages, and activated neutrophils, and is immobile due to the glycosylphosphatidylinositol tail [10; 11]. The circulating form found in serum and other body fluids, is thought to be the result of protease-mediated shedding/cleavage of mCD14 [12]. sCD14 provides cells such as fibroblasts, and epithelial and endothelial cells that lack the membrane bound form of CD14, a sensitivity to bacterial products [12]. Thus, ultimately both mCD14 and sCD14 can function as a receptor for LPS of gram-negative bacteria and for various cell wall products of gram-positive bacteria [10]. In addition to its role in LPS/cell wall products signaling, sCD14 might play a part in inflammatory diseases by regulating the immune systems response [13]. In periodontal derived mesenchymal stromal cells, sCD14 drastically enhances inflammatory response to various bacterial components, such as lipopolysaccharideacharide, lipoteichoic acid, and lipoproteins [14; 15].  
Since CD14 is an important regulator of the inflammatory response to bacteria, it is hypothesized to play an essential role in regulating periodontitis pathogenesis. However, the exact role of CD14 in periodontal health and periodontitis is not well defined. This systematic review aims to examine the currently available literature with reference to CD14 and periodontitis, focusing on how its role pertains to the pathogenesis of periodontitis. This review explicitly explores the levels of expression of mCD14 and sCD14 in peripheral blood monocytes, saliva, gingival circular fluid, and gingival tissue biopsies to allow a more in-depth understanding of the mechanism of periodontitis and provide information for future outcome measures for periodontal disease.