Collagens of most connective tissues are subject to continuous remodelling and turnover, a phenomenon which occurs under both physiological and pathological conditions. Degradation of these proteins involves participation of a variety of proteolytic enzymes including members of the following proteinase classes: matrix metalloproteinases (e.g. collagenase, gelatinase and stromelysin), cysteine proteinases (e.g. cathepsin B and L) and serine proteinases (e.g. plasmin and plasminogen activator). Convincing evidence is available indicating a pivotal role for matrix metalloproteinases, in particular collagenase, in the degradation of collagen under conditions of rapid remodelling, e.g. inflammation and involution of the uterus. Under steady state conditions, such as during turnover of soft connective tissues, involvement of collagenase has yet to be demonstrated. Under these circumstances collagen degradation is likely to take place particularly within the lysosomal apparatus after phagocytosis of the fibrils. We propose that this process involves the following steps: (i) recognition of the fibril by membrane-bound receptors (integrins?), (ii) segregation of the fibril, (iii) partial digestion of the fibril and/or its surrounding non-collagenous proteins by matrix metalloproteinases (possibly gelatinase), and finally (iv) lysosomal digestion by cysteine proteinases, such as cathepsin B and/or L. Modulation of this pathway is carried out under the influence of growth factors and cytokines, including transforming growth factor beta and interleukin 1 alpha.

Guided bone regeneration (GBR) is frequently used in oral implantology. It is unclear to what extent GBR affects the periodontium of adjacent teeth. Therefore, the present study quantifies changes in the proximal gingiva and bone levels at these teeth in 30 patients. Staged surgery involved a standard GBR treatment, randomly using resorbable membranes with a bone substitute or non-resorbable membranes with or without a bone substitute, followed by fixture installation at 6 months and abutment connection a further 6 months later. The data were sampled at each surgery and analysed using MANOVA. Twelve months after GBR, there was on average a small but statistically significant amount of proximal gingival recession (0.75 mm) and bone resorption (0.34 mm) observed, of which 50% was the result of GBR surgery. No significant differences were found between the different GBR treatment modalities. It is concluded that GBR treatment may have a small negative effect on the levels of the free gingival margin and alveolar bone at adjacent teeth, which is in most patients not clinically relevant.

Cytokines modulate routes of collagen breakdown: review with special emphasis on mechanisms of collagen degradation in the periodontium and the burst hypothesis of periodontal disease progression van der Zee, E.; Everts, V.; Beertsen, W. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract. In this paper, we review recent work on collagen degradation, 2 main routes of breakdown are described and their relevance during healthy and inflammatory conditions of the periodontium is discussed. Special attention is paid to the possible role of cytokines, in particular interleukin 1 (IL-1) and transforming growth factor /? (TGF-^). on the modulation of collagen phagocytosis and metalloproteinase production. IL-1 has been shown to have a dual function in collagen digestion. It inhibits the intracellular phagocytic pathway, but at the same time, it strongly promotes extracellular digestion by inducing the release of collagenolytic enzymes like collagenase, TGF-^ has an opposite effect on both pathways and antagonizes IL-1, Collagenase is released in an inactive form, and a considerable fraction of the proenzyme may become incorporated in the extracellular matrix. This reservoir of latent enzyme can be activated (for instance by plasmin), leading to a sudden and extensive breakdown of the collagenous fibre meshwork. It is suggested that this phenomenon may also take place during progressive periodontitis and could explain an episodic nature of collagenolysis, clinically resulting in bursts of attachment loss (burst hypothesis).

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Periodontal-like tissues and, in particular, alveolar bone- and root cementum-like material can theoretically be modulated by release of biochemical agents such as bisphosphonate (PCP), growth hormone (GH) and alkaline phosphatase (ALP) from the implant surface. The present research focused on porous ceramic hydroxyapatite (PCHA) implants. In the past the PCHA implants were machined on a lathe out of simple blocks of PCHA ceramic. This was a tedious and cumbersome method, often resulting in implants with undesirable characteristics: different porosities, cracks and fractures. Therefore a moulding technique was developed to sinter near-net-shaped PCHA implants at 2 different sintering temperatures: 1170 degrees C and 1280 degrees C, resulting in PCHA implants with porosities of 62.06% (PCHA type 1) and 40.74% (PCHA type 2), respectively. After 1 h incubation in a 10(-2) M solution of PCP, the total amounts adsorbed onto PCHA type 1 and type 2 were 114.9 +/- 2.1 micrograms and 46.1 +/- 1.5 micrograms, respectively. This was approximately 5 times higher than after incubation for 1 wk in a 10(-4) M solution of PCP. The total amounts of PCP released after the observation period of 75 d from PCHA type 1 and type 2 after incubation in the 10(-2) M solution were 103.1 +/- 1.8 micrograms and 42.8 +/- 1.5 micrograms, respectively. The total amounts released from type 1 and 2 after incubation in the 10(-4) M solution were 7.4 +/- 0.4 micrograms and 4.1 +/- 0.1 micrograms, respectively. After 2 wk of incubation in a liver/bone/kidney ALP solution the total amount of ALP adsorbed onto PCHA type 1 implants was 5039 +/- 412 mU/ml. The total amounts of ALP released were 4674 +/- 438 mU/ml and 53 +/- 20 mU/ml after 1 and 2 wk, respectively. The release of ALP was high at the beginning but slowed down thereafter. It was evident that despite the well-known high bonding affinity of PCP to HA the release of PCP occurred steadily, over a long period of time in vitro.

The present study comprises an investigation of 7 different probe types, representing currently-marketed major designs (WHO-CPITN, Williams, Michigan), as well as available calibration systems (engraved, etched and painted markings). Width of markings, accuracy of calibration from probe tip, and tine diameter at the tip and at specified points along the tine were assessed, using a stereomicroscope at a magnification of x 40. Blind duplicate measurements of these probe tine characteristics were 100% reproducible to within 0.01 mm. There was an overall range in marking width from 0.00-1.13 mm. The best marking, in that it had no appreciable width and the highest accuracy, was the discrete transition between normal and engraved parts of probes with engraved bands. Mean inaccuracies of different probe sets varied from 0.06 to 0.22 mm. Probes from the same batch from the same production line could differ by more than 0.5 mm in calibration. Mean tip diameter ranged from 0.28 to 0.70 mm. It was concluded that probe tine diameter and calibration should be considered in addition to other variables of periodontal probing. Standardisation of tine characteristics and avoidance of the use of different types or batches in a single study should enhance the accuracy and reproducibility of periodontal probe-dependent measurements.

It is concluded that the presented method makes it possible to evaluate reproducibly and accurately changes in gingiva and bone levels for GBR studies.

Degradation of fibrillar collagen may occur in the extracellular space by enzymes, such as the metalloproteinase collagenase, or in the lysosomal apparatus of fibroblasts following phagocytosis. As the mechanisms involved in the regulation of the latter process are unknown, we investigated possible modulating effects of the cytokines epidermal growth factor (EGF), platelet-derived growth factor (PDGF), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta) on both collagen phagocytosis and the release of collagenase in an in vitro model employing periosteal tissue explants. The data demonstrated that the level of intracellular collagen digestion could be influenced by cytokines: IL-1 alpha inhibited and TGF-beta enhanced phagocytosis of fibrillar collagen by periosteal fibroblasts, whereas the cytokines had an opposite effect on the release of procollagenase. In combination, IL-1 alpha and TGF-beta proved to have an antagonizing effect on either parameter. PDGF and EGF had no effect on phagocytosis or collagenase release. The level of phagocytosed collagen correlated positively with the actual breakdown of collagen as assessed by the release of hydroxyproline but negatively with the level of released procollagenase. Our findings demonstrated that cytokines are able to modulate both the phagocytosis of collagen fibrils by fibroblasts and their subsequent intracellular breakdown, as well as the release of procollagenase, an enzyme considered crucial for extracellular collagenolysis. Moreover, our data show a negative correlation between these two parameters. It is concluded that IL-1 alpha, EGF and TGF-beta may be important in modulating the contribution of the intracellular and extracellular route of collagen breakdown.