Increased surface roughness of dental implants has demonstrated greater bone apposition; however, the effect of modifying surface chemistry remains unknown. In the present study, we evaluated bone apposition to a modified sandblasted/acid-etched (modSLA) titanium surface, as compared with a standard SLA surface, during early stages of bone regeneration. Experimental implants were placed in miniature pigs, creating 2 circular bone defects. Test and control implants had the same topography, but differed in surface chemistry. We created the test surface by submerging the implant in an isotonic NaCl solution following acid-etching to avoid contamination with molecules from the atmosphere. Test implants demonstrated a significantly greater mean percentage of bone-implant contact as compared with controls at 2 (49.30 vs. 29.42%; p = 0.017) and 4 wks (81.91 vs. 66.57%; p = 0.011) of healing. At 8 wks, similar results were observed. It is concluded that the modSLA surface promoted enhanced bone apposition during early stages of bone regeneration.
Abstract. Agrin is a basal lamina protein that induces aggregation of acetylcholine receptors (AChRs) and other molecules at the developing neuromuscular junction. Alternative splicing of chick agrin mRNA at two sites, A and B, gives rise to eight possible isoforms of which five are expressed in vivo. Motor neurons express high levels of isoforms with inserts at sites A and B, muscle cells synthesize isoforms that lack amino acids at the B-site. To obtain further insights into the mechanism of agrin-induced AChR aggregation, we have determined the ECs0 (effective concentration to induce half-maximal AChR clustering) of each agrin isoform and of truncation mutants. On chick myotubes, ECs0 of the COOH-terminal, 95-kD fragment of agrinA4a8 was ,'~35 pM, of agrinA4aZ9 ~110 pM and of agrinA4a, --5 nM. While some AChR clusters were observed with 64 nM of agrinA4aO, no activity was detected for agrinAoa0. Recombinant fulllength chick agrin and a 100-kD fragment of ray agrin showed similar ECso values. A 45-kD, COOH-terminal fragment of agrinA4u retained high activity (ECso ----130 pM) and a 21-kD fragment was still active, but required higher concentrations (ECs0 ---13 nM). Unlike the 45-kD fragment, the 21-kD fragment neither bound to heparin nor did heparin inhibit its capability to induce AChR aggregation. These data show quantitatively that agrinA4nS and agrinA4mg, expressed in motor neurons, are most active, while no activity is detected in agrinAoBo, the dominant isoform synthesized by muscle cells. Furthermore, our results show that a fragment comprising site Bs and the most COOHterminal G-like domain is sufficient for this activity, and that agrin domains required for binding to heparin and those for AChR aggregation are distinct from each other.T HE formation of chemical synapses in the nervous system requires exchange of local signals between preand postsynaptic cells. At the neuromuscular junction (NMJ) ~, muscle cells aggregate several proteins, such as acetylcholine receptors (AChRs), acetylcholinesterase, and heparan sulfate proteoglycans at the site of contact between nerve and muscle cell. This process is, at least in part, initiated by the release of molecules from the motor axon. Several lines of evidence suggest that agrin, a component of synaptic basal lamina, is such a molecule. On cultured myotubes, agrin induces aggregation of several molecules that are concentrated at the NMJ including AChRs (Nitkin et al., 1987;Wallace, 1989). Motor neurons synthesize agrin, transport it to the nerve terminal from where it is released to induce AChR aggregation (Magill
Agrin is a heparan sulfate proteoglycan that induces aggregation of acetylcholine receptors (AChRs) at the neuromuscular synapse. This aggregating activity is modulated by alternative splicing. Here, we compared binding of agrin isoforms to heparin, alpha-dystroglycan, and cultured myotubes. We find that the alternatively spliced 4 amino acids insert (KSRK) is required for heparin binding. The binding affinity of agrin isoforms to alpha-dystroglycan correlates neither with binding to heparin nor with their AChR-aggregating activities. Moreover, the minimal fragment sufficient to induce AChR aggregation does not bind to alpha-dystroglycan. Nevertheless, this fragment still binds to cultured muscle cells. Its binding is completed only by agrin isoforms that are active in AChR aggregation, and therefore this binding site is likely to represent the receptor that initiates AChR clustering.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.