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Bruno Frediani

Publications and source records attributed to Bruno Frediani.

11 recordsLinked to original sources
PubMed2006

Osteogenic growth peptide effects on primary human osteoblast cultures: potential relevance for the treatment of glucocorticoid-induced osteoporosis.

The osteogenic growth peptide (OGP) is a naturally occurring tetradecapeptide that has attracted considerable clinical interest as a bone anabolic agent and hematopoietic stimulator. In vivo studies on animals have demonstrated that the synthetic peptide OGP (10-14), reproducing the OGP C-terminal active portion [H-Tyr-Gly-Phe-Gly-Gly-OH] increases bone formation, trabecular bone density and fracture healing. In vitro studies performed on cellular systems based on osteoblastic-like cell lines or mouse stromal cells, have demonstrated that OGP (10-14) increases osteoblast proliferation, alkaline phosphatase (ALKP) activity and matrix synthesis and mineralization. In view of a potential application of OGP (10-14) in clinical therapy, we have tested different concentrations of OGP (10-14) on primary human osteoblast (hOB) cultures. We have observed significant increases of hOB proliferation (+35%), ALKP activity (+60%), osteocalcin secretion (+50%), and mineralized nodules formation (+49%). Our experimental model based on mature hOBs was used to investigate if OGP (10-14) could prevent the effects on bone loss induced by sustained glucocorticoid (GC) treatments. A strong decrease in bone formation has been attributed to the effects of GCs on osteoblastogenesis and osteocyte apoptosis, while an increase in bone resorption was due to a transient osteoblastic stimulation, mediated by the OPG/RANKL/RANK system, of osteoclasts recruitment and activation. Moreover, GCs act on hOBs decreasing the release of osteoprotegerin (OPG) a regulator of the RANKL/RANK interaction. Here, we provide evidences that OGP (10-14) inhibits hOB apoptosis induced by an excess of dexamethasone (-48% of apoptotic cells). Furthermore, we show that OGP (10-14) can increase OPG secretion (+20%) and can restore the altered expression of OPG induced by GCs to physiological levels. Our results support the employment of OGP (10-14) in clinical trials addressed to the treatment of different bone remodeling alterations including the GC-induced osteoporosis.

Aged↗
PubMed2006

Vascular endothelial growth factor-D activates VEGFR-3 expressed in osteoblasts inducing their differentiation.

Vascular endothelial growth factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that recognizes and activates the vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 on blood and/or lymphatic vessels. We show that in the long bones of newborn mice, VEGF-D and VEGFR-3 are expressed in the osteoblasts of the growing plate. The treatment of primary human osteoblasts with recombinant VEGF-D induces the expression of osteocalcin and the formation of mineralized nodules in a dose-dependent manner. A monoclonal neutralizing antibody, anti-VEGF-D, or silencing of VEGFR-3 by lentiviral-mediated expression of VEGFR-3 small hairpin RNA affects VEGF-D-dependent osteocalcin expression and nodule formation. Moreover, in primary human osteoblasts, VEGF-D expression is under the control of VEGF, and inhibition of VEGF-D/VEGFR-3 signaling, by monoclonal antibodies or VEGFR-3 silencing, affects VEGF-dependent osteoblast differentiation. These experiments establish that VEGF-D/VEGFR-3 signaling plays a critical role in osteoblast maturation and suggest that VEGF-D is a downstream effector of VEGF in osteogenesis.

Aged↗
PubMed2006

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.

Adult↗
PubMed2006

Novel therapeutic agents for bone resorption. Part 1. Synthesis and protonation thermodynamics of poly(amido-amine)s containing bis-phosphonate residues.

Two poly(amido-amine)s (oligoPAM and oligoNER) containing bis-phosphonate residues were obtained by a Michael-type polyaddition of pamidronate and neridronate to 1,4-bis(acryloyl)piperazine. The SEC (size-exclusion chromatography) and the MALDI-TOF (matrix assisted laser desorption ionization) analyses were consistent with the presence of oligomeric species (2-3 kDa) and with a narrow polydispersity index. The thermodynamic results (log Ks, -DeltaH(o) , and DeltaS(o) obtained at 25 degrees C in 0.15 M NaCl) of both the oligomers and the corresponding low molecular weight precursors were in line with a cluster structure formed during the protonation of the basic nitrogen in the pamidronate. The solubility of the oligoNER with a longer aliphatic chain was improved at high pHs, allowing the evaluation of their solution properties. Preliminary biological results show that both the oligomers do not negatively affect the in vitro viability, proliferation, and cellular activity of either normal animal or human osteoblasts.

Bone Resorption↗
PubMed2004

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.

Aged↗
PubMed2004

Effects of high dose methylprednisolone pulse therapy on bone mass and biochemical markers of bone metabolism in patients with active rheumatoid arthritis: a 12-month randomized prospective controlled study.

OBJECTIVE: To study the effects of one year of high dose 6-methylprednisolone pulse therapy (MPPT) on bone mass, seric bone alkaline phosphatase (sBAP), and urinary deoxypyridinoline (uDpyr) in patients with active rheumatoid arthritis (RA), and to compare results with those of patients with active RA treated with oral methylprednisolone (OMP). METHODS: Thirty-one women with active RA were given 1000 mg of MP IV for 3 alternate days, with a mean interval of administration of 76 days (+/- 8.3 SD) for one year (MPPT group). Bone mineral density (BMD) (total body, lumbar spine, and femur neck), plasma levels of sBAP, and urinary concentrations of uDpyr were assessed at the beginning of the treatment and every 3 months until the end of the study. Moreover, erythrocyte sedimentation rate (ESR), Thompson joint score, and early morning stiffness were assessed at study entry and every month. The control group, 31 women with active RA treated with oral MP, was followed in the same way (OMP group). RESULTS: In the MPPT group there was no significant reduction of BMD at any site compared to significant reductions in lumbar BMD at 6 and 12 months and total body BMD and femur neck BMD at 12 months in the OMP group. Also in the OMP group, a significant reduction in the mean sBAP was observed. The mean uDpyr levels were not significantly reduced in either group. CONCLUSION: Our results show that MPPT, compared to continuous therapy with oral corticosteroids, preserves bone mass without modifying the biochemical markers of bone metabolism.

Absorptiometry, Photon↗
PubMed2004

Ultrasonographic study of Achilles tendon and plantar fascia in chondrocalcinosis.

OBJECTIVE: To investigate by high frequency grey-scale ultrasonography (US) and power Doppler sonography (PDS) the modality and frequency of involvement of the Achilles tendon and plantar fascia in chondrocalcinosis (CC), and to correlate these findings with clinical complaints and radiographic evidence. METHODS: The heels of 57 consecutive patients with CC were evaluated by US, PDS, and radiography. One control group of 50 consecutive patients with osteoarthritis (OA) without signs of CC was studied in the same way. A second control group of 50 healthy subjects underwent only US/PDS examination. All subjects also underwent clinical assessment. RESULTS: US revealed Achilles tendon calcifications in 57.9% of those with CC, but none in the control groups. Plantar fascia calcifications were observed in 15.8% of CC and in 2% of OA cases, but not in healthy controls. US showed no significant difference in postero-inferior and inferior calcaneal enthesophytosis between subjects with CC (59.6% and 61.4%, respectively) and those with OA (46% and 44%, respectively). Such alterations were also present, in lower percentages, in the healthy controls. Posterior and inferior calcaneal erosions were absent in all groups. Achilles enthesopathy was found in 22.8% of patients with CC (14.9% of heels, with vascular signals in 11.4% of heels on PDS). Deep retrocalcaneal bursitis was found in 10.5% of patients with CC (7% of heels, with vascular signals in 5.2% of heels on PDS). Plantar fasciitis was found in 40.3% of patients with CC (36% of heels, with vascular signals in 2.6% of heels on PDS) and in 14% of OA patients, but not in healthy controls. No significant correlation was found between talalgia or sex of patients and presence of calcifications. A significant correlation was observed between talalgia and Achilles enthesopathy (r = 0.78, p < 0.0001), deep retrocalcaneal bursitis (r = 0.7, p < 0.0001), and plantar fasciitis (r = 0.31, p < 0.001). A significant correlation between talalgia and vascular signals on PDS was observed in Achilles enthesopathy (r = 0.91, p < 0.0001) and deep retrocalcaneal bursitis (r = 0.65, p < 0.0001). The presence of vascular signals on PDS was significantly associated with the presence of tendinous and bursal grey-scale US alterations. Achilles tendon calcifications were 39% sensitive, 100% specific, and 77% accurate for the presence of CC, whereas plantar fascia calcifications were 15% sensitive, 98% specific, and 54% accurate. Excellent agreement was found between US and radiography in detecting Achilles tendon calcifications (k = 0.86), plantar fascia calcifications (k = 0.77), postero-inferior enthesophytosis (k = 0.90), and inferior enthesophytosis (k = 0.83). CONCLUSION: Calcaneal tendon calcifications are frequent and asymptomatic findings in patients with CC, and they have a high specificity for this disease. US shows high agreement with radiography in depicting calcifications and enthesophytosis. Inflammatory changes of the calcaneal soft tissues are frequently observed by US and PDS in patients with chondrocalcinosis.

Achilles Tendon↗
PubMed2002

Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients with psoriatic arthritis and rheumatoid arthritis.

Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone, and it is a fundamental element in the diagnosis of spondyloarthropathies. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and the late alterations (erosions and enthesophytes); it is also an inexpensive, biologically harmless and easily repeatable technique. The aim of this study was to compare the prevalence of quadricipital enthesitis in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document any clinical and echostructural differences in this lesion between the two diseases. The results show that enthesitis is more frequent in PsA patients, more than half of whom are asymptomatic. Knee inflammation was found in the PsA patients with enthesitis regardless of the concomitant presence of joint effusion; none of the RA patients suffered from enthesitis alone. Quadricipital enthesitis is more frequent in male patients. There was no significant correlation between the presence of peripatellar psoriatic lesions and enthesitis. Sonographic examinations of patients with enthesitis revealed that those with RA had dominantly inflammatory lesions, whereas PsA patients also showed major new bone deposition.

Arthritis, Psoriatic↗
PubMed2002

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.

Age Factors↗
PubMed2002

Enthesitis of proximal insertion of the deltoid in the course of seronegative spondyloarthritis. An atypical enthesitis that can mime impingement syndrome.

OBJECTIVE: To study the frequence of deltoideal proximal insertion enthesitis (DPIE) in patients affected with spondyloarthritis (SpA) and to evaluate its clinical, sonographic and radiological characteristics. METHODS: A retrospective study of clinical, sonographic and radiological examinations of the shoulders of 100 symptomatic consecutive outpatients with SpA, compared to 4 groups of control patients: 100 with Rheumatoid Arthritis, 100 with Osteoarthritis, 100 with Painful Shoulder, and 50 with shoulders undamaged by local pathological processes. RESULTS: The frequence of DPIE in the course of SpA was 9%. DPIE appears most frequently in Psoriatic Arthritis (PsA) (17%, 7/41). DPIE does not appear to be related to the sex or the age of the patient. The clinical signs and symptoms are similar to those of an impingement syndrome. Sonography reveals thickening and hypoechogenicity of the enthesis, associated or not to the subchondral osseous rearrangement and enthesophytosis. Radiology only reveals the enthesophytosis in the later stages. CONCLUSIONS: DPIE can determine shoulder pain in the course of SpA, and in particular in PsA. The clinical manifestations of DPIE are very similar to those of an impingement syndrome; sonography can differentiate the two conditions.

Adult↗