Although the biological significance of proteoglycans (PGs) has previously been highlighted in multiple myeloma (MM), little is known about serglycin, which is a hematopoietic cell granule PG. In this study, we describe the expression and highly constitutive secretion of serglycin in several MM cell lines. Serglycin messenger RNA was detected in six MM cell lines. PGs were purified from conditioned medium of four MM cell lines, and serglycin substituted with 4-sulfated chondroitin sulfate was identified as the predominant PG. Flow cytometry and confocal microscopy showed that serglycin was also present intracellularly and on the cell surface, and attachment to the cell surface was at least in part dependent on intact glycosaminoglycan side chains. Immunohistochemical staining of bone marrow biopsies showed the presence of serglycin both in benign and malignant plasma cells. Immunoblotting in bone marrow aspirates from a limited number of patients with newly diagnosed MM revealed highly increased levels of serglycin in 30% of the cases. Serglycin isolated from myeloma plasma cells was found to influence the bone mineralization process through inhibition of the crystal growth rate of hydroxyapatite. This rate reduction was attributed to adsorption and further blocking of the active growth sites on the crystal surface. The apparent order of the crystallization reaction was found to be n ؍ 2, suggesting a surface diffusion-controlled spiral growth mechanism. Our findings suggest that serglycin release is a constitutive process, which may be of fundamental biological importance in the study of MM.
Poly(vinyl chloride-co-vinyl acetate-co-maleic acid) (vinyl chloride 83%, vinyl acetate 13%, carboxylated
1%) was found to be a substrate favoring the deposition of vaterite crystals from stable supersaturated
solutions at pH 8.50 and 25 °C. Induction times preceding calcium carbonate precipitation were inversely
proportional to the solution supersaturation, and a surface energy of 23 mJm-2 was calculated according
to classical nucleation theory. The relatively low value may be attributed to the heterogeneous character
of vaterite nucleation. The linear dependence of the rates of vaterite formation on the solution
supersaturation, in which the crystallization took place, in combination with the independence of the
measured rates on the fluid dynamics, suggested that vaterite overgrowth was controlled by surface diffusion.
This finding was in agreement with the results obtained for the crystallization of vaterite on cholesterol.
Our results suggest that the kinetics of overgrowth may be very important for the stabilization of transient
mineral phases. The structure of the polymeric substrates also plays a role, mainly through the development
of active growth sites, which should show chemical and structural affinity to the mineral phase.
Four natural amino acids with hydrophobic nonpolar side group (alanine, phenylalanine, proline, and methionine) were examined and their activity on hydroxyapatite, HAP, crystallization was assessed. The method used was the constant composition technique, at low supersaturation levels. Crystallization took place exclusively on well-characterized HAP seed crystals introduced in supersaturated solutions only with respect to the calcium phosphate salt. The fit of the experimental data to the Langmuir adsorption isotherm indicates an inhibition mechanism based upon molecular adsorption of the amino acids on the HAP crystal surface at active growth sites. The inhibitory effect was related to the adsorption affinity constant of each amino acid to the crystal surface, which depends on the nature of the amino acids' side group.
Four copolymers were prepared through the reaction of NN-bis[ (diethoxyphosphinyl)methyl]-1,4benzenediamine with 1,4-or 1,3-benzenediamine and terephthaloyl or isophthaloyl or sebacoyl dichloride at varying molar ratios. A fifth copolymer was prepared by copolymerization of bis(3-aminopheny1)phoephinic acid and 1,3-benzenediamine with ieophthaloyl dichloride in dimethylamine. All five copolymers contained phosphinyl groups and upon introduction in calcium phosphate aqueous solutions, supersaturated only with respect to 8-tricalcium phosphate and hydroxyapatite, three of them induced the precipitation of stoichiometric hydroxyapatite, (Caa(PO&OH, HAP). The investigation of the crystal growth process was done at constant supersaturation, which enabled us to measure even very low rates of crystallization. The apparent growthorder was found to be 1.25 f 0.18, avalue found for the crystallization of HAP on various substrates. The surface energy estimate of 92 mJ m-? from the kinetic data was of the same order of magnitude for the overgrowth of HAP on both inorganic and polymeric substrates. The rates of precipitation showed a linear dependence on the phosphate content of each copolymer, while their structure played b o a decisive role. Thus, "open" structured copolymers yielded high rates of precipitation while copolymers in which the phosphorus-containing groups were "buried", not being accessible to the Ca2+ ions in solution, failed to induce hydroxyapatite formation. It is suggested that the phosphoruscontaining groups act as the active centers for nucleation of the inorganic phase. (34) Glimcher, M. J. In The Chemistry and Biology of Mineralized Cinnetuue Tissues; Vein, A,, Ed.; Ehvier: Amstardam, 1981; pp 617-675. (35) Glimcher, M.
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