Long-term effects of neridronate on human osteoblastic cell cultures.

UNLABELLED: Bisphosphonates (BPs) are widely used in the treatment of a variety of bone-related diseases, particularly where the bone turnover is skewed in favor of osteolysis. The mechanisms by which BPs reduce bone resorption directly acting on osteoclasts are now largely clarified even at molecular level. Researches concerning the BP's effects on osteoblast have instead shown variable results. Many in vitro studies have reported positive effects on osteoblasts proliferation and mineralization for several BPs; however, the observed effects differ, depending on the variety of different model system that has been used. OBJECTIVES: We have investigated if neridronate, an aminobisphosphonate suitable for pulsatory parenteral administration, could have an effect on human osteoblastic proliferation and differentiation in vitro. METHODS: We have investigated whether prolonged addition of neridronate (from 10(-3) to 10(-11) M) to different human osteoblasts cultures, obtained from 14 different bone specimens, could affect the cells number, the endogenous cellular alkaline phosphatase (ALKP) activity, and the formation of mineralized nodules. RESULTS: Our results show that neridronate does not negatively affect in vitro the viability, proliferation, and cellular activity of normal human osteoblasts even after a long period addition of the drug (20 days) at concentrations equal or lower than 10(-5) mol/l (therapeutic dose). In addition, neridronate seems to enhance the differentiation of cultured osteoblasts in mature bone-forming cells. A maximum increase of alkaline phosphatase activity (+50% after 10 days; P < 0.01) and mineralized nodules (+48% after 20 days; P < 0.05) was observed in cultures treated with neridronate 10(-8) M. CONCLUSIONS: These results encourage the use of neridronate in long-term therapy of demineralizing metabolic bone disorders.

A proteomic study on human osteoblastic cells proliferation and differentiation.

Changes in expression profiles for 17 proteins were ascertained in human mature osteoblasts compared to pre-osteoblasts (differentiation markers). A differential approach was used to highlight proteomic changes between human osteosarcoma cells and mature osteoblasts, showing a relative over-expression of 8 proteins (proliferation and tumor indicators), as well as under-expression of proteins also found down-regulated in pre-osteoblasts (specific markers of osteoblast differentiation). Our findings confirmed the differences between cell lines and primary human cell cultures and suggested caution on the use of osteosarcoma to study anti-osteoporotic drugs in humans.

Evidence for synovitis in active polymyalgia rheumatica: sonographic study in a large series of patients.

OBJECTIVE: To determine the frequency and localization of synovitis and enthesitis in patients with active, untreated polymyalgia rheumatica (PMR) by ultrasonography (US). METHODS: Polyarticular sonographic evaluation was carried out in 50 consecutive patients with PMR at disease onset. Results were compared with 50 consecutive patients with seronegative spondyloarthropathies (SpA) and 50 with seronegative and seropositive rheumatoid arthritis (RA) at disease onset. RESULTS: Synovitis and/or effusion was detected, in at least one joint, in 100% of patients with PMR. The most frequent alterations observed in patients with PMR were effusion in the subacromial-subdeltoid (SA-SD) bursa in 70% of patients, tenosynovitis of the long head of the biceps tendon (LHBT) in 68%, glenohumeral joint effusion in 66%, tenosynovitis of the flexor tendons in the carpal tunnel in 38%, radiocarpal effusion in 18%, wrist extensors tenosynovitis in 18%, coxofemoral joint effusion in 40%. knee effusion in 38%, and ankle effusion in 10%. Enthesitis and tendonitis of the anchoring tendons were relatively rare in all the articular sites. Comparison of the SpA and PMR patients showed that enthesitis (mostly in the elbow, knee, and heel) was significantly more frequent in SpA. There was a significant difference in glenohumeral and coxofemoral effusion between the PMR and SpA patients (66% vs 16% and 40% vs 14%, respectively). Comparison of PMR and RA patients showed no significant difference in the involvement of entheses, shoulder, hip, or wrist flexor tendons in the carpal tunnel. Synovitis of the elbow, knee, and wrist was significantly more frequent in the SpA and RA patients than in those with PMR. CONCLUSION: Synovitis was detected in at least one site in 100% of patients with PMR. SA-SD bursitis, LHBT tenosynovitis, carpal tunnel syndrome, and glenohumeral, knee and hip synovitis were the most frequent alterations in PMR. Enthesitis was relatively rare at any articular site.

Presence of macrophage migration inhibitory factor in human milk: evidence in the aqueous phase and milk fat globules.

Human milk is a source of bioactive substances regulating the development and activity of the newborn immune system. Human milk has been found to contain a number of cytokines, including interleukins, growth factors, and colony stimulating factors. In the present study, we assessed 10 specimens of human milk for the presence of macrophage migration inhibitory factor (MIF), a cytokine recently described in several human reproductive organs and tissues. Using biochemical as well as immunologic techniques, we showed that MIF is abundantly present in human milk, mostly distributed in the lipid layer and in the aqueous phase. Fractionation of the lipid layer showed that MIF is highly concentrated inside milk fat globules. In view of its proinflammatory features, we speculate that milk MIF may protect the newborn against infection and play a role in preserving the functionality of the lactating mammary gland. Furthermore, the localization of MIF in lipid globules suggests a possible strategy for the protection of milk cytokines from the gastric barrier.