Role of fibroblasts in periodontium
Collagen degradation
*Intracellular collagen profiles* within the cytoplasm Extracellular collagen is phagocytosed
Fibroblast-synthesised structural proteins
- Collagen - Oxytalin/elastin fibres - Intermediate cytoskeleton fibres - *Vimentin* - Ground substance - GAGs, proteoglycans, glycoproteins *Fibronectin* - glycoprotein, attachment of cells to collagen *Integrin* - glycoprotein cell surface receptor
Gingival fibrosis
- Faster than bone and skin turnover, slower than PDL. - Granulation tissue forms - Granulation tissue fibroblasts - clonal population essential to proper collagen remodelling which may be deleted by apoptosis during healing - Fibroblast cells specialising in rapid collagen synthesis are retained --> FIBROSIS
Increase in collagen in gingival fibrosis could be due to?
- Increase in collagen formation - Decrease in collagen degradation - Survival/proliferation of fibroblasts
Loss of collagen in periodontal disease could be due to?
- Increase rate of collagen degradation - Decreased rate of collagen formation - Decreased amount of fibroblasts
Where do fibroblasts receive signals from?
- Inflammatory cells such as *macrophages or lymphocytes* - Bacteria - Mechanical force - Phagocytosed collagen - ECM of bone, cementum or periodontal tissues - Paracrine or autocrine loops
Migration/contraction of fibroblasts in wound healing
- Migrate into wound and proliferate. - Synthesis components of ECM - Close wound by contractile forces on collagen fibres
Collagen turnover and mechanical loading
- Minor reversible inflammatory reactions occur
Fibroblasts
- Multiple points of contact via *desmosomes & gap junctions* - Cytoplasmic processes envelop collagen fibres - Active cells rich in *intracytoplasmic organelles* associated with synthesis and export of proteins
Fibroblast cell functions
- Synthesis, secretion & *degradation* of proteins - Proliferation & apoptosis - Migration - Contraction - Interact with other fibroblasts or different cell types present in the PDL or gingivae
Half-life of collagen
6-9 days. Has high turnover
How can fibroblasts influence *osteoclast* activity?
Can inhibit and support osteoblast differentiation and function. - OPG inhibits resorption - RANKL stimulates resorption
PDLSCs, what can they produce?
Cementoblasts Fibroblasts Osteoblasts IDEAL THERAPY
How is PDL width maintained?
Control extent of osteogenesis and cementogenesis during physiological remodelling of periodontium Disruption can lead to *ankylosis* (which can be induced with bisphosphonate treatment)
Fibroblast cell turnover
Fibroblast proliferation increases in response to trauma, inflammation, sustained mechanical loading *PDLSCs* Mitotic index is modest in normal Periodintal tissue, decreases with age
When are PGs and ATP production induced by fibroblasts?
Following mechanical load or PD disease. May influence bone activity
Migration/contraction of fibroblasts in vitro
Mostly from in vitro work - not representative. method of culture influences data
Migration of fibroblasts
Some evidence Needs *chemotactic stimuli* e.g. extracts from bone and cementum New populations must migrate to their site of action
What factors can regulate the proliferation & differentiation of fibroblasts, osteoblasts and cementoblasts and promote angiogenesis?
TGFβ , IGF-1, PDGF, BMP-2, BMP-7 and FGF-2 Used in animal models to promote periodontal regeneration.
Features of PDL fibroblasts
• Have a different *embryological origin* (gingival fibroblasts have mesenchymal origin) • *Do not* have contact with *overlying epithelial cells* • Have a *higher rate of cell proliferation* • Secrete *more* collagen *type III* • Demonstrate a faster rate of *collagen turnover* • Have an *increased cell volume* • Secrete *less ground substance* • Express *more alkaline phosphatase & cAMP* • Contain *more contractile proteins*