Papers by Jean-Louis Saffar
Histamine participates in the early phase of trabecular bone loss in ovariectomized rats

Journal de biologie buccale, 1986
This study describes episodes of rapid destruction and repair of periodontal tissues occurring du... more This study describes episodes of rapid destruction and repair of periodontal tissues occurring during the course of hamster periodontitis. The mandibular molar periodontia of 120 male golden hamsters exposed to Keyes 2000 diet for periods ranging from 45 to 180 days were examined on undecalcified serial sections. The destructive phase of the episodes was characterized by the localized appearance of a large number of osteoclasts creating a cone-shaped defect. Bone resorption was associated with disorganization of the gingival tissues, including epithelial ulceration, and a dense PMN infiltration. The repair phase was observed in these cone-shaped defects by the use of fluorescent and corresponding stained sections. Bone formation was intense with woven bone filling the cervical aspect of the defect. Apically, bone formation was more regular and less rapid. A healthy band of connective tissue always separated the bone reaction from the infiltrated connective tissue. Despite its magnit...

Journal de biologie buccale, 1986
Since macroscopic bone loss in hamster periodontitis appears to be a continuous process, this stu... more Since macroscopic bone loss in hamster periodontitis appears to be a continuous process, this study was undertaken to evaluate whether osteoclastic resorption is continuously activated or whether another pattern of activation occurred during the course of the disease. At the beginning of the experimental period, 5 male golden hamsters were killed; they were used as to controls. Forty other animals were then distributed into 2 equal groups. In the experimental group, periodontitis was induced by using the Keyes 2000 diet. Five animals in both control and experimental groups were killed at 45, 90, 135 and 180 days. The following parameters were quantitated in the mandibles: - the macroscopic bone loss, - the number of osteoclasts in contact or lying at a distance from bone, and - the number of nuclei per mm of bone surface. Control animals developed spontaneous, slowly progressing periodontitis. In the experimental animals, osteoclasts were more numerous along the periosteum than alon...
Journal de biologie buccale, 1979
The purpose of this study was to analyze through morphometric analysis, the variations of the end... more The purpose of this study was to analyze through morphometric analysis, the variations of the endosteal bone balance during experimental periodontal disease induced in the golden hamster. The results showed that the osteoclastic resorption is increased by a factor of 5 (p less than 0.01) and the bone formation reduced by about 50% (p less than 0.01). The bone volume decreased slightly (by 6%) but significantly (p less than 0.01). No correlation between respectively resorption and formation and bone volume was found.

Journal of Periodontal Research, 1985
This study was undertaken to follow the changes in bone remodeling during the progress of periodo... more This study was undertaken to follow the changes in bone remodeling during the progress of periodontitis in the hamster. The comparison of quantitative and morphological data showed that the disease is associated with an important disturbance of the remodeling process. The development of bone resorption, preceded by the arrest of the physiological bone formation, is associated with an increase in the extent in reversal (= empty) lacunae. Bone fonnation refilled only a small number of these lacunae, although in some cases the formation reaction could be vigorous. These events coexisted and reoccurred with marked variations in space and in time, regardless of the time of exposure to the disease. Moreover, the onset at the bone level of the disease was characterized by an initial and precocious increase in bone volume, immediately subjacent to the inflammed gingival tissues.

Calcified Tissue Research, 1976
Alveolar bone is a very good model for studying bone remodelling and the cellular events involved... more Alveolar bone is a very good model for studying bone remodelling and the cellular events involved in remodelling. The reason why it is easier to use this bone than long bones is that in all mammals teeth move spontaneously, throughout the life time of the animal, in a mesial direction in man and in the monkey, and in a distal direction in rodents. For this reason, alveolar bone offers both a high turnover rate and an oriented activity: one side of the socket is undergoing continuous bone formation and the opposite side undergoes bone remodelling. In previous studies (Baron, 1973a, b) we described the aspects of both the bone formation and the remodelling sequence occurring within small foci along the remodelling side.of the sockets. This sequence is composed of four steps; firstly, bone resorption occurs and creates a focus; the focus is then occupied by mononucleated cells during the reversal phase; these mononucleated cells become osteoblasts, which partially fill the focus during the formation phase; and, finally, a resting phase occurs before the onset of a new remodelling sequence in the same area. Using different fluorescent labellings (tetracycline, calcein, orange xylenol and alizarin red S) with different intervals, it has been demonstrated that, in the lower molar area in the adult rat, the daily rate of bone formation on the modelling side of the sockets is 4.7 +__ 0.3/am (Guyomard and Baron, 1974). This side is therefore continuously covered by a layer of osteoblasts and osteoid tissue, as shown by 4/am thick undecalcified sections. As far as the periodontal ligament width, between the root and the bone surface, remains constant in these animals, we know consequently that the net balance of the remodelling sequence is minus 4.7 + 0.3/am/day. Using undecalcified sections, 4/am thick, the extent of the different cellular activities involved in this remodelling sequence was measured. Bone resorption, i.e. Howship's lacunae with osteoclasts in close contact with bone, covers 14 +_ 4% of the surface; the reversal step, i.e. lacunae without osteoclasts, covers 31 +_. 4%;

Calcified Tissue Research, 1977
This study was carried out on adult golden hamsters, to correlate the effects of porcine calciton... more This study was carried out on adult golden hamsters, to correlate the effects of porcine calcitonin on serum Ca and P concentrations with changes in osteoclastic resorption of bone. After 1 month of treatment with 5 M1RC units/kg/day, there was little effect on these parameters. On the other hand, the hormone appears to have an effect on the remodelling sequence, as indicated by a large and very significant decrease in the extent of resorption lacunae unoccupied by osteoelasts. It is suggested that the duration of the reversal phase, separating the end of active resorption from the beginning of active bone formation in each remodelling focus, is greatly decreased. This shortening is associated with a prolongation oft he bone formation phase, and the extent of osteoid tissue is markedly and proportionally increased in the treated animals. After a prolonged administration, caleitonin does not seem to impede the formation of new osteoclasts, their number being only slightly diminished, but it remains possible that it does continue to inactivate these cells. The effect on the bone remodelling sequence could be either due to direct action on the osteoblasts or their precursor cells, or an indirect action via the osteoelasts.
Archives of Oral Biology, 1982

Archives of Oral Biology, 1982
Osteoclast activity in terms of number, nucleus content and position in relation to bone surface ... more Osteoclast activity in terms of number, nucleus content and position in relation to bone surface features was quantitated during experimental periodontal disease. The increase in total osteoclast population, particularly on periosteal rather than endosteal surfaces, was due mainly to the number of cells in direct contact with the bone surface (on-bone osteoclasts). On-bone cell nuclei per mm of bone surface was constantly significantly greater in experimental animals than in controls. There was a positive linear relationship between the extent of resorbing surface and the nucleus content of the on-bone osteoclasts. Thus, in experimental periodontal disease, increases in the number of on-bone osteoclasts are responsible for the changes in the total number of these cells and disease activity is expressed more accurately by the number of nuclei of on-bone osteoclasts per mm of bone surface.

Calcified Tissue International, 2005
Essential fatty acids (EFAs) play a significant role in bone metabolism. Herein we studied the ad... more Essential fatty acids (EFAs) play a significant role in bone metabolism. Herein we studied the adaptation of alveolar bone to physiologic tooth drift in young rats deprived of essential fatty acids from birth. Reductions in femur size and trabecular bone volume reflected body growth impairment. Along the alveolar wall, osteoclastic resorption and bone formation were depressed, disrupting the adaptive deformation of the tooth socket to ongoing migration. As a result, the periodontal ligament narrowed considerably, and further adaptation was achieved through root resorption. Essential fatty acid deficiency (EFAD), did not affect precursor recruitment or differentiation in the periodontal ligament (PDL), but caused redistribution of nonspecific-esterase (NSE)-positive osteoclast precursors and tartrate-resistant acid phosphatase (TRAP)positive preosteoclasts between the bone compartment (which was depleted) and the root compartment (which was enriched). EFAD had also a marked effect on the PDL vasculature; the number of vessels was reduced, whereas their size was markedly increased. As a whole, our results show that EFAD disturbs alveolar bone adaptation to drift, but that a reaction (detrimental to root integrity) prevents root collision with the bone surface, thereby preserving the PDL as a source of precursor cells for bone and cementum homeostasis. Moreover, our results confirm that although alveolar bone resorption is arachidonic acid-dependent, the factors activating root resorption are different.
La presente invention se rapporte a l'utilisation de fucanes de masse molaire moyenne en poid... more La presente invention se rapporte a l'utilisation de fucanes de masse molaire moyenne en poids comprise entre 5'000 et 100'000 g/mol a des fins de greffe, d'ingenierie et de regeneration osseuses.

Heliyon, 2017
The activation step of bone remodeling remains poorly characterized. Activation comprises determi... more The activation step of bone remodeling remains poorly characterized. Activation comprises determination of the site to be remodeled, osteoclast precursor recruitment, their migration to the site of remodeling, and differentiation. These actions involve different compartments and cell types. The aim of this study was to investigate events and cell types involved during activation. We used a bone remodeling model in rats where extractions of the upper jaw molars initiate remodeling of the antagonist lower jaw (mandible) cortex along the periosteum. In this model osteoclastic resorption peaks 4 days after extractions. We previously reported that mast cell activation in the periosteum fibrous compartment is an early event of activation, associated with recruitment of circulating monocyte osteoclast precursors. By using immunohistochemistry, we observed 9 hours after induction a spatially oriented expression of InterCellular Adhesion Molecule-1 in the vessels that was inhibited by antago...

Journal of cellular physiology, 2018
In bone remodeling, osteoclasts are recruited via increased production of RANKL (receptor activat... more In bone remodeling, osteoclasts are recruited via increased production of RANKL (receptor activator of nuclear factor-κB ligand) and migrate to the bone surface, aided by matrix metalloproteinases (MMPs). NAMPT (nicotinamide phosphoribosyl transferase), which catalyzes the rate-limiting step in the NAD salvage pathway, increases during in vitro osteogenic differentiation and inhibits RANKL-induced osteoclast differentiation. Alveolar bone loss, due to disturbance of the remodeling process, is a major feature of periodontitis. Thus, we investigated the role of NAMPT in a synchronized alveolar bone remodeling rat model. NAMPT expression increased in osteogenic cells during the remodeling activation phase, in parallel with RANKL and MMP-2 expression. Inhibition of NAMPT activity, by systemic delivery of its selective inhibitor FK866, decreased the recruitment of osteoclasts, but not their activity. In vitro, NAMPT mRNA, and protein expression also increased during osteoblast differenti...

Glycoconjugate journal, Jun 7, 2016
The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is h... more The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic injury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of the ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury disrupts this delicate equilibrium and may impair the wound healing process. ReGeneraTing Agents (RGTA(®)s) are polysaccharides specifically designed to replace degraded HS in injured tissues. The unique properties of RGTA(®) (resistance to degradation, binding and protection of ECM structural and signaling proteins, like HS) permit the reconstruction of the ECM, restoring both structural and biochemical functions to this essential substrate, and facilitating the processes of tissue repair and regeneration. Here, we review 25 years of research surrounding this HS mimic, supporting the m...
Journal of Dentistry, 2016
Pre-prosthetic use of poly(lactic-co-glycolic acid) membranes treated with oxygen plasma and TiO ... more Pre-prosthetic use of poly(lactic-co-glycolic acid) membranes treated with oxygen plasma and TiO 2 nanocomposite particles for guided bone regeneration processes'
<b>Copyright information:</b>Taken from "Prostaglandin E2 synthesis in cartilage... more <b>Copyright information:</b>Taken from "Prostaglandin E2 synthesis in cartilage explants under compression: mPGES-1 is a mechanosensitive gene"Arthritis Research &amp; Therapy 2006;8(4):R135-R135.Published online 27 Jul 2006PMCID:PMC1779392. Mouse articular cartilage explants were compressed (C) or not (NC) for 2 h, 4 h, 18 h and 24 h. The amount of PGEreleased into the media (pg/ml) was measured by enzyme immunoassay. Values are the mean ± SEM of 2 independent experiment with = 2/group/experiments, analyzed in duplicate. *p &lt; 0.05, **p &lt; 0.01, ***p &lt; 0.001 versus control (NC).

<b>Copyright information:</b>Taken from "Prostaglandin E2 synthesis in cartilage... more <b>Copyright information:</b>Taken from "Prostaglandin E2 synthesis in cartilage explants under compression: mPGES-1 is a mechanosensitive gene"Arthritis Research &amp; Therapy 2006;8(4):R135-R135.Published online 27 Jul 2006PMCID:PMC1779392. Mouse costal cartilage explants were compressed (C) or not (NC) for 2 h, 4 h, 18 h and 24 h. At each time interval, our results are expressed in fold-induction in comparison to the appropriate control. The amount of NO released into the media (μmol/mg of costal cartilage) was measured by Griess reagent. Values are the mean and SEM of 3 (C 2 h and 4 h) and 2 (C 18 h and 24 h) independent experiments with = 2/group/experiments. ***p &lt; 0.001 versus control (NC). The amount of PGEreleased into the media (pg/mg/ml of costal cartilage) was measured by enzyme immunoassay. Values are the mean and SEM of 3 (C 2 h), 2 (C 4 h and 18 h) and 4 independent experiments (C 24 h) with = 2/group/experiments, analyzed in duplicate. ***p &lt; 0.001 versus control (NC).
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Papers by Jean-Louis Saffar