A new approach to treat tissue destruction in periodontitis with chemically modified dextran polymers.

Periodontitis are diseases of the supportive tissues of the teeth provoked by bacteria and characterized by gingival inflammation and bone destruction. We have developed a new strategy to repair tissues by administrating agents (RGTA) that mimic heparan sulfates by protecting selectively some of the growth factors naturally present within the injured tissue and interfering with inflammation. After periodontitis induction in hamsters, the animals were left untreated or received weekly i.m. injections of RGTA1507 at a dose of 100 microg/kg, 400 microg/kg, 1.5 mg/kg, or 15 mg/kg for 4 wk. RGTA treatment significantly reduced gingival tissue inflammation, thickened the pocket epithelium by increasing cell proliferation, and enhanced collagen accumulation in the gingiva. A marked reduction in bone loss was observed, resulting from depression of osteoclasia and robust stimulation of bone formation at the dose of 1.5 mg/kg. RGTA treatment for 8 wk at this dose reversed macroscopic bone loss, sharply contrasting with the extensive bone destruction in the untreated animals. RGTA treatment decreased gelatinase A (MMP-2) and B (MMP-9) pro-forms in gingival tissues. Our data indicate that a 4 wk treatment dose-dependently attenuated gingival and bone manifestations of the disease, whereas a longer treatment restored alveolar bone close to controls. By modulating and coordinating host responses, RGTA has unique therapeutic properties and is a promising candidate for the treatment of human periodontitis.

Chemical sympathectomy-induced changes in TH-, VIP-, and CGRP-immunoreactive fibers in the rat mandible periosteum: influence on bone resorption.

The expression of neurotransmitter receptors by bone cells supports the concept that the nervous system is a regulator of bone metabolism. The discrimination of the respective roles of the sensory and sympathetic nervous systems requires evidence of topographic relationships between the corresponding fibers and the cells involved in bone turnover, in vivo. In this study, the influence of the sympathetic system on bone resorption was assessed by using a synchronized model of cortical resorption along the mandible. The sympathetic system was destroyed by daily injections of guanethidine (40 mg/kg) for 25 days; a resorption wave was induced on day 21. The distribution of periosteal tyrosine-hydroxylase (TH)-, vasoactive intestinal polypeptide (VIP)-, and calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fibers was studied by compartmentalizing the periosteum. Most fibers were located in the distal, non-osteogenic compartment. TH-IR fibers were located perivascularly, VIP-IR fibers were gathered at the boundary with the osteogenic compartment, and CGRP-IR fibers were scattered. Sympathectomy decreased the number of TH- and VIP-IR fibers and increased the number of CGRP-IR fibers, without changing their topography. After the injection of Fast blue, a retrograde fluorescent marker, over the periosteum, fluorescent neuronal cell bodies were found in the superior cervical ganglion (SCG). Many neurons were TH-IR and very few were VIP-IR. Sympathectomy decreased the numbers of fluorescent and TH-IR cell bodies. It also decreased the number of preosteoclasts and osteoclasts, which had a drastic effect on the cortical bone surface, as assessed by scanning electron microscopy. These data indicate that VIP-IR fibers have a strategic position close to the most peripheral and less differentiated, osteogenic cells, pointing to a functional relationship. As poorly differentiated osteogenic cells support preosteoclast differentiation, VIP-IR fibers may be involved in this process, as suggested by the smaller number of preosteoclasts in sympathectomized rats. Although VIP is predominantly a parasympathetic mediator, it seemed to be conveyed by sympathetic fibers, as shown by the marked effect of guanethidine treatment. Nevertheless, these fibers did not originate from the SCG, contrary to TH-IR fibers.