Proteoglycans synthesized by cultured fibroblasts derived from normal and inflamed human gingiva

Abstract

The in vitro proliferations rates and proteoglycans synthesized by adult human gingival fibroblasts derived from six age- and sex-matched donors of healthy and chronically inflamed gingiva were analyzed. Fibroblasts from inflamed gingiva demonstrated a slower growth rate than cells from healthy tissue. The rate of incorporation of [35S]sulfate into cell layer-associated proteoglycans and the release of these macromolecules into the culture medium did not differ appreciably between the two groups of cells. Similarly, no detectable differences in the overall charge of the proteoglycans synthesized by normal and inflamed gingival fibroblasts, as assessed by their elution from DEAE-Sephacel, were noted. However, Sepharose CL-4B chromatography revealed that the medium-associated proteoglycans made by the inflamed tissue fibroblasts were depleted in one species of chondroitin sulfate proteoglycans and contained more dermatan sulfate than did control cells. In addition, the intracellular proteoglycan pool was found to be greatly diminished in the inflamed tissue fibroblast cell layers. Glycosaminoglycan analysis of the proteoglycans confirmed these observations. Compared to normal gingival fibroblasts, the inflamed tissue fibroblasts released less heparan sulfate into the medium. Additionally, increased levels of dermatan sulfate and depleted amounts of chondroitin sulfate in the medium of inflamed gingival cells were noted. The observed changes were stable through several transfers in culture and indicate that chronically inflamed tissue may contain fibroblasts manifesting a heritable phenotype differing from fibroblasts in normal connective tissue.

Isolation and characterization of gingival fibroblasts positive for alkaline phosphatase in patients with chronic periodontitis and drug-induced gingival hyperplasia

“…These findings are similar to those observed by Abe et al (11) and demonstrate that in CP, gingival fibroblasts have low potential for growth. This is also consistent with previous in vitro studies showing reduced proliferative capacity for fibroblasts from chronically inflamed human gingiva and periodontium (11)(12)(13). However, with the exception of Abe et al, all studies, including ours, did not use phenotypic markers for identification of fibroblasts in inflamed tissues.…”

Control of tissue homeostasis by the extracellular matrix: Synthetic heparan sulfate as a promising therapeutic for periodontal health and bone regeneration

“…Loss of heparan sulfate proteoglycans on the surface of cells from patients with an inflamed periodontium was confirmed in subepithelial and subendothelial basement membranes and in infiltrating leukocytes 195 . When fibroblasts collected from healthy versus diseased gingiva were cultured, the fibroblasts from inflamed tissue secreted less heparan sulfate and more dermatan sulfate, a phenotype that persisted after several cell culture passages, demonstrating longevity of the phenotype 196 …”

“…195 When fibroblasts collected from healthy versus diseased gingiva were cultured, the fibroblasts from inflamed tissue secreted less heparan sulfate and more dermatan sulfate, a phenotype that persisted after several cell culture passages, demonstrating longevity of the phenotype. 196 In different cells of the periodontium, periodontal ligament, gingival fibroblasts and osteoblasts, syndecan-2 exhibited a significant difference in expression. The presence of specific cell surface proteoglycans on periodontal cells implies distinctive functions.…”

Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis

“…Non-fibrous ECM components are other glycoproteins, glycosaminoglycans (but neither keratan sulphate nor chondroitin sulphate 6 were found in the gingival connective tissue), and corresponding proteoglycans, forming the gel in which the structural fibrous components and cells are embedded [ 15 , 33 , 129 , 136 , 137 ]. All glycosaminoglycans identified in human gingiva and the other ECM components are synthesized by gingival fibroblasts [ 137 , 138 , 139 ], with the exception of blood vessels. The gingival lamina propria contains also cellular components like fibroblasts, mastocytes, granulocytes, monocytes, macrophages, dendritic cells, lymphocytes, natural killer cells, and gingival mesenchymal stem cells; some of them are absent or not activated until microbial accumulation or invasion occur [ 15 , 140 , 141 , 142 , 143 , 144 ].…”