We isolated and expanded BMSCs from human alveolar/jaw bone at a high success rate (70%). These cells had potent osteogenic potential in vitro and in vivo, although their chondrogenic and adipogenic potential was less than that of iliac cells.Introduction: Human bone marrow stromal cells (BMSCs) have osteogenic, chondrogenic, and adipogenic potential, but marrow aspiration from iliac crest is an invasive procedure. Alveolar BMSCs may be more useful for regenerative medicine, because the marrow can be aspirated from alveolar bone with minimal pain. Materials and Methods: In this study, alveolar bone marrow samples were obtained from 41 patients, 6-66 years of age, during the course of oral surgery. BMSCs were seeded and maintained in culture with 10% FBS and basic fibroblast growth factor. In addition, BMSCs were induced to differentiate into osteoblasts, chondrocytes, or adipocytes in appropriate medium. Results and Conclusion: From a small volume (0.1-3 ml) of aspirates, alveolar BMSCs expanded at a success ratio of 29/41 (70%). The success rate decreased with increasing donor age, perhaps because of age-dependent decreases in the number and proliferative capacity of BMSCs. The expanded BMSCs differentiated into osteoblasts under osteogenic conditions in 21-28 days: the mRNA levels of osteocalcin, osteopontin, and bone sialoprotein, along with the calcium level, in alveolar BMSC cultures were similar to those in iliac cultures. However, unlike iliac BMSC, alveolar BMSC showed poor chondrogenic or adipogenic potential, and similar differences were observed between canine alveolar and iliac BMSCs. Subsequently, human alveolar BMSCs attached to ␤-tricalcium phosphate were transplanted into immunodeficient mice. In transplants, new bone formed with osteoblasts and osteocytes that expressed human vimentin, human osteocalcin, and human GAPDH. These findings suggest that BMSCs have distinctive features depending on their in vivo location and that alveolar BMSCs will be useful in cell therapy for bone diseases.

We have demonstrated that the angiotensin-converting enzyme (ACE) genotype is associated with Alzheimer's disease (AD) in the Japanese population (1). To determine why ACE affects susceptibility to AD, we examined the effect of purified ACE on aggregation of the amyloid ␤-peptide (A␤) in vitro. Surprisingly, ACE was found to significantly inhibit A␤ aggregation in a dose response manner. The inhibition of aggregation was specifically blocked by preincubation of ACE with an ACE inhibitor, lisinopril. ACE was confirmed to retard A␤ fibril formation with electron microscopy. ACE inhibited A␤ deposits on a synthaloid plate, which was used to monitor A␤ deposition on autopsied brain tissue. ACE also significantly inhibited A␤ cytotoxicity on PC12 h. The most striking fact was that ACE degraded A␤ by cleaving A␤-(1-40) at the site Asp 7 -Ser 8 . This was proven with reverse-phase HPLC, amino acid sequence analysis, and MALDI-TOF/MS. Compared with A␤-(1-40), aggregation and cytotoxic effects of the degradation products A␤-(1-7) and A␤-(8 -40) peptides were reduced or virtually absent. These findings led to the hypothesis that ACE may affect susceptibility to AD by degrading A␤ and preventing the accumulation of amyloid plaques in vivo.Progressive cerebral dysfunction in Alzheimer's disease (AD) 1 is accompanied by innumerable extracellular amyloid deposits in the form of senile plaque and microvascular amyloid. Amyloid protein is derived from the integral membrane polypeptide, ␤-amyloid precursor protein (␤APP). The released 39 -43 residue amyloid ␤-peptide (A␤) may subsequently undergo aggregation to form amyloid fibrils under the influence of various amyloid-associated factors (2). The aggregation and deposition of A␤ has been linked to the toxic effects causing cell damage in AD. Because A␤ is present in both normal and AD subjects, an answer to the question of why A␤ accumulates in AD but not in the normal brain may lead to a possible cure for AD.Angiotensin-converting enzyme (ACE; dipeptidyl carboxypeptidase, EC 3.4.15.1) is a membrane-bound ectoenzyme. It catalyzes the conversion of angiotensin I (AngI) to angiotensin II (AngII), which plays an important role in blood pressure and body fluid and sodium homeostasis (3). The cloning of the ACE gene revealed a 287-bp insertion (I)/deletion (D) polymorphism in intron 16. The serum ACE activity of the ACE DD genotype was twice as high as that of the ACE II genotype (4). The ACE genotype is considered to be associated with hypertension, coronary artery disease, left ventricular hypertrophy, myocardial infarction, and diabetic nephropathy (5-7). In particular, the ACE DD genotype is considered to be a risk factor for vascular diseases.We have compared the distribution of an I/D polymorphism of the gene coding for ACE in 133 Japanese sporadic AD patients and 257 control subjects (1). The association between AD and ACE genotypes or alleles was found to be significant. The frequency of the ACE II genotype was 1.4ϫ higher in AD than in controls, whereas that of ACE DD gen...

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There are inflammatory cytokines in facet joint tissue at high levels in degenerative lumbar spinal disorders. Inflammatory cytokines have a higher concentration rate in lumbar spinal canal stenosis than in lumbar disc herniation. This finding suggests that inflammatory cytokines in degenerated facet joints may have some relation to the cause of pain in degenerative lumbar disorders.

We reported recently that angiotensin-converting enzyme (ACE) significantly degraded amyloid beta-peptide (A beta) to inhibit aggregation and cytotoxicity of A beta in PC12h cells in vitro. On the other hand, others reported that ACE had two domains with highly homologous active centres, the N-domain and C-domain, but that they differed in their characteristics such as optimum chloride ion concentration, inhibition kinetics for various ACE inhibitors and rate of hydrolysis for many substrates. The aim of this study was to determine the specific ACE domain primarily responsible for degradation of A beta. For this purpose, a series of ACE recombinant proteins, each containing only one intact domain, was constructed and expressed in COS7. Our results showed that all ACE recombinant proteins obtained were enzymatically active in terms of angiotensin I cleavage. However, inhibition of A beta aggregation and cytotoxicity of the N-domain were higher than those of the C-domain. Reverse-phase high-performance liquid chromatography analyses confirmed that the N domain degraded A beta. Our results indicate that the N domain of ACE is primarily responsible for the degradation of A beta.