Distribution And Expression Of Fibromodulin In Normal Periodontium, Inflamed Gingiva And During Periodontal Wound Healing

Intense microbiological, immunological and biochemical investigations in recent years have been done to determine the precise aetiological and pathological events associated with the periodontal disease, whereas treatment regimes have not always advanced at a commensurate rate. Once tissue destruction has occured, the ultimate goal of periodontal therapy should be regeneration of the affected tissues to restore their original architecture and function. Despite many of the shortfalls of current therapies, each development has been useful and has permitted a better understanding of the complex events associated with peridontal healing and regeneration. Proteoglycans promise to be a useful tool in the control of cell behaviors such as those critical to the successful repair of a wound.Fibromodulin is one of the members of the leucine-rich repeat protein family. Other principal members from the same family are biglycan, decorin, lumican, etc. This group of proteoglycan is closely related to collagen with similar structure. They can interact with each other in extracellular matrix and be involved in the regulation of tissue events. A few studies on fibromodulin have been done, but few refer to periodontium aspect. The aim of this thesis was to demonstrate immunolocalization of fibromodulin in normal periodontium, inflamed gingiva and during periodontal wound healing, and the role of fibromodulin in periodontium would be elucidated. In the meantime, other small proteoglycans such as biglycan and decorin, as well as type I and type III collagens, would be compared with fibromodulin.The experiments were carried out in four parts.Part one was to study distribution and expression of fibromodulin in normal periodontium, so as to understand better the role of fibromodulin in periodontal tissues homeostasis. Tissuedistribution and cellular localization of fibromodulin were evaluated by immunohistochemical methods in normal Lewis rat molar periodontium using antibody for fibromodulin. mRNA expression of fibromodulin in human periodontal cells (gingival fibroblasts, periodontal ligament fibroblasts and osteoblasts) was measured by reverse transcription-polymerase chain reaction and further semiquantified by NIH gel analysis program. Our results demonstrated that fibromodulin distributed in suprabasal gingival epithelium, gingival and periodontal fibroblasts as well as their matrices. Strong expression was noted in the area close to oral aspect of gingiva and the interfaces of periodontal ligament-alveolar bone and periodontal ligament-cementum. By comparison, decorin and biglycan, which were from the same family as fibromodulin, showed different distribution and association with collagen fibrils. Decorin was strongly expressed in the area close to the gingival sulcus in gingival tissue. Biglycan was stained evidently in gingival epithelium. Observed from mRNA expression, fibromodulin was expressed very strongly in osteoblasts which also showed a stronger expression for decorin and biglycan. mRNA of type I and type III collagens were detected higher levels in gingival fibroblasts than osteoblasts and periodontal ligament fibroblasts. Specific distribution and expression of fibromodulin in the periodontal tissues and cells suggest that fibromodulin might interact with other small proteoglycans to regulate the network formation of periodontal collagen fibers, and might be involved in mineralization of alveolar bone and cementum.Part two was to study distribution and expression of fibromodulin in human healthy gingiva and inflamed gingiva from gingivitis and periodontitis. The aim was to investigate the altered expression of fibromodulin in inflamed gingiva. Gingival specimens were obtained from healthy human as well as gingivitis and periodontitis patients. Immunohistochemial analyses were carried out to detect the distribution of fibromodulin in healthy and inflamed gingiva. The results showed that fibromodulin did not stain obviously in healthy gingival connective tissue, however stained strongly in inflamed connective t...