https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673604166270.pdf

Investigation of multipotent postnatal stem cells from human periodontal ligament

Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells and certain other cell types. It is a dimeric molecule consisting of disulfide-bonded, structurally similar A- and B-polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms exert their cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors, denoted the alpha-receptor and the beta-receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the actin filament system and stimulates chemotaxis, i.e., a directed cell movement toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactivity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecule. Similarly, overproduction of PDGF may be involved in autocrine and paracrine growth stimulation of human tumors. Overactivity of PDGF has, in addition, been implicated in nonmalignant conditions characterized by an increased cell proliferation, such as atherosclerosis and fibrotic conditions. This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues.

https://www.physiology.org/doi/pdf/10.1152/physrev.1999.79.4.1283

Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor

Periodontitis, or gum disease, affects millions of people each year. Although it is associated with a defined microbial composition found on the surface of the tooth and tooth root, the contribution of bacteria to disease progression is poorly understood. Commensal bacteria probably induce a protective response that prevents the host from developing disease. However, several bacterial species found in plaque (the 'red-complex' bacteria: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) use various mechanisms to interfere with host defence mechanisms. Furthermore, disease may result from 'community-based' attack on the host. Here, I describe the interaction of the host immune system with the oral bacteria in healthy states and in diseased states.

Periodontitis: a polymicrobial disruption of host homeostasis

http://www.endoexperience.com/documents/Cellularmolecularandtissuelevelreactionstoorthoforce_2006.pdf

Cellular, molecular, and tissue-level reactions to orthodontic force

II. CHARACTERISTICS OF INFLAMMATORY PROCESSES 75 A. Physical Changes 75 1. Vascular Dynamics 75 2. Immigration of Leukocytes and Macrophages 75 3. Proliferation of Fibroblasts 75 B. Chemical Changes 76 1. Cyclic Nucleotides 76 2. Mediators 76 a. Histamine 76 b. Serotonin 76 c. Brady kinin 76 d. Prostaglandins 77 3. Proteolytic Activity 77 III. COMPARISON BETWEEN OVULATION AND INFLAMMATION 78 A. Vascular Dynamics 78 1. In Ovulation 78 2. In Inflammation 78 B. Leukocytes and Macrophages 79 1. In Ovulation 79 2. In Inflammation 79 C. Fibroblasts 80 1. In Ovulation 80 2. In Inflammation and Related Processes 80 D. Cyclic Nucleotides 81 1. In Ovulation 81 2. In Inflammation and Related Processes 82 E. Steroids 83 1. In Ovulation 83 2. In Inflammation and Related Processes 84

Ovulation as an Inflammatory Reaction—A Hypothesis

Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology.

Molecular and cell biology of the gingiva

The effects of prostaglandin E2 (PGE2) upon the synthesis of protein and DNA, and membrane transport of proline and thymidine, by human diploid fibroblasts were studied. At a concentration range of 1-10 μM, PGE2 inhibited protein synthesis and membrane transport by 45-50%. Serum-activated DNA synthesis and thymidine transport were also inhibited by approximately 50% in cells made quiescent and synchronous by serum deprivation. To determine whether prostaglandin inhibits some of the cells completely or all of the cells partially, radioautographic and cell-counting experiments were done. In cultures pulse-labeled with [3H]thymidine 12-33 hr after serum activation, prostaglandin exposure reduced the number of labeled nuclei by 42%. Sixty-five hours after serum activation, the total cell numbers present in the PGE2-exposed cultures were reduced by 25%. Furthermore, in the fibroblast cultures derived from cells previously maintained in 10 μM PGE2 for 14 days, PGE2 had no effect on DNA synthesis, indicating that the PGE2-sensitive cells had disappeared from the cultures. Thus, PGE2 appears to inhibit growth and synthesis of a subpopulation of cells while not affecting the remaining insensitive cells. Prostaglandins may play an important role in connective-tissue differentiation and in some pathologic alterations by regulating fibroblast subpopulations.

Fibroblast heterogeneity and prostaglandin regulation of subpopulations.

Cementum forms the interface through which soft connective tissue of the periodontium is attached to the root surface. The interactions between cementum and connective tissue are not completely understood and whether cementum influences periodontal connective tissue formation and regeneration is not clear. We have examined the effect of cementum components on the attachment of gingival fibroblasts. Cementum was harvested from healthy human and bovine teeth and extracted sequentially in 0.5 M CH3COOH, 4 M guanidine and bacterial collagenase. Fibroblast attachment was measured using 51Cr-labelled human gingival fibroblasts on tissue culture plates previously incubated with cementum components. Results showed that all three extracts mediated fibroblast attachment and attachment was dependent on concentration and incubation time. The attachment activity was not destroyed by digestion with bacterial collagenase or by antibodies to fibronectin and laminin. However, it was inhibited by a peptide containing the amino acid sequence RGD. By gel filtration or HPLC using a DEAE-cellulose column several proteins with attachment activity were fractionated. SDS-polyacrylamide gel electrophoresis revealed that HPLC fraction eluted by 0.2–0.3 M NaCl contained a protein with molecular weight 55 kDa as a major component. This protein was isolated and shown to promote fibroblast attachment, and optimal attachment occurred at a concentration of 2 μg/ml. We conclude that cementum contains substances capable of mediating fibroblast attachment and that these substances play an important role in periodontal connective tissue formation and regeneration by facilitating fibroblast attachment to root surfaces.

Isolation of a fibroblast attachment protein from cementum

Cementum is continuously formed during the lifetime of a tooth. The paravascular zones in the adult periodontal ligament (PL) comprise the progenitors for the fibroblastic (Fb) lineage and mineralized tissue-forming (MTF) cell lineages--the osteoblastic (Ob) and cementoblastic (Cb) lineages. Recent studies indicate that cementum attachment protein (CAP) is related to the differentiation of the Cb lineage and is instrumental in differentiating between the three periodontal cell lineages. The purpose of this study was to assess the effect of bone morphogenetic protein 2 (BMP2) on the expression of cementum attachment protein (CAP) and on the differentiation of cloned PL progenitors. The effect of BMP2 on CAP expression and on the differentiation of cloned Fb and MTF progenitors was tested by assessing the expression of alkaline phosphatase (ALP), CAP, and bone sialoprotein (BSP) by immunochemistry and by determining the CAP-binding capacity of these clones. Untreated Fb clones were negative for all tested m...

A. S. Narayanan

Papers

Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology.

Molecular and cell biology of the gingiva

Fibroblast heterogeneity and prostaglandin regulation of subpopulations.

Isolation of a fibroblast attachment protein from cementum

Bone Morphogenetic Protein 2 Induces the Expression of Cementum Attachment Protein in Human Periodontal Ligament Clones