The most significant results in experimental and clinical orthopaedic research in Italy within the last three years have been primarily in major congenital diseases, bone tumors, regenerative medicine, joint replacements, spine, tendons and ligaments. The data presented in the following discussion is comparable with leading international results, highlighting Italian orthopaedic research excellemce as well as its shortcomings.
PazzagliaUECongiuTMarcheseMDell'OrboC. The shape modulation of osteoblast-osteocyte transformation and its correlation with the fibrillar organization in secondary osteons: A SEM study employing the graded osmic maceration technique. Cell Tissue Res2010; 340: 533–40.
2.
LisignoliGCodeluppiKTodoertiKManferdiniCPiacentiniAZiniNGrassiFCattiniLPivaRRizzoliVFacchiniAGiulianiNNeriA. Gene array profile identifies collagen type XV as a novel human osteoblast-secreted matrix protein. J Cell Physiol2009; 220:401–9.
3.
GaudioAPennisiPBratengeierCTorrisiVLindnerBMangiaficoRAPulvirentiIHawaGTringaliGFioreCE. Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab2010; 95:2248–53.
4.
LambertiniELisignoliGTorreggianiEManferdiniCGabusiEFranceschettiTPenolazziLGambariRFacchiniAPivaR. Slug gene expression supports human osteoblast maturation. Cell Mol Life Sci2009; 66:3641–53.
GrassiFManferdiniCCattiniLPiacentiniAGabusiEFacchiniALisignoliG. T cell suppression by osteoclasts in vitro. J Cell Physiol2010 Sep 20. [Epub ahead of print]
7.
FerlinAPepeAFacciolliAGianeselloLForestaC. Relaxin stimulates osteoclast differentiation and activation. Bone2010; 46:504–13.
8.
TortelliFPujicNLiuYLarocheNVicoLCanceddaR. Osteoblast and osteoclast differentiation in an in vitro three-dimensional model of bone. Tissue Eng Part A2009; 15:2373–83.
9.
PangrazioACaldanaMESobacchiCPanaroniCSusaniLMihciECavaliereMLGilianiSVillaAFrattiniA. Characterization of a novel Alu-Alu recombination-mediated genomic deletion in the TCIRG1 gene in five osteopetrotic patients. J Bone Miner Res2009; 24:162–7.
10.
Del FattoreAFornariRVan WesenbeeckLde FreitasFTimmermansJPPeruzziBCapparielloARucciNSperaGHelfrichMHVan HulWMigliaccioSTetiA. A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts. J Bone Miner Res2008; 23:380–91.
11.
GuerriniMMSobacchiCCassaniBAbinunMKilicSSPangrazioAMorattoDMazzolariEClayton-SmithJOrchardPCoxonFPHelfrichMHCrockettJCMellisDVellodiATezcanINotarangeloLDRogersMJVezzoniPVillaAFrattiniA. Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. Am J Hum Genet2008; 83:64–76.
12.
CapparielloABerardiACPeruzziBDel FattoreAUgazioABottazzoGFTetiA. Committed osteoclast precursors colonize the bone and improve the phenotype of a mouse model of autosomal recessive osteopetrosis. J Bone Miner Res2010; 25:106–13.
13.
TondelliBBlairHCGuerriniMPatreneKDCassaniBVezzoniPLucchiniF. Fetal liver cells transplanted in utero rescue the osteopetrotic phenotype in the oc/oc mouse. Am J Pathol2009; 174:727–35.
14.
DominiciMMarinoRRasiniVSpanoCPaolucciPContePHofmannTJHorwitzEM. Donor cell-derived osteopoiesis originates from a self-renewing stem cell with a limited regenerative contribution after transplantation. Blood2008; 111:4386–91.
15.
PanaroniCGioiaRLupiABesioRGoldsteinSAKreiderJLeikinSVeraJCMertzELPerilliEBaruffaldiFVillaIFarinaACasascoMCettaGRossiAFrattiniAMariniJCVezzoniPForlinoA. In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta. Blood2009; 114:459–68.
16.
GranchiDDevescoviVBaglìoSRLeonardiEDonzelliOMagnaniMStilliSGiuntiABaldiniN. Biological basis for the use of autologous bone marrow stromal cells in the treatment of congenital pseudarthrosis of the tibia. Bone. 2010; 46:780–8.
17.
FalchettiADi StefanoMMariniFOrtolaniSUlivieriMFBerguiSMasiLCepollaroCBenucciMDi MunnoORossiniMAdamiSDel PuenteAIsaiaGTorricelliFBrandiML; GenePage Project. Genetic epidemiology of Paget's disease of bone in italy: Sequestosomel/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone. Calcif Tissue Int2009; 84:20–37.
18.
GennariLGianfrancescoFDi StefanoMRendinaDMerlottiDEspositoTGalloneSFuscoPRaineroIFenoglioPManciniMMartiniGBerguiSDe FilippoGIsaiaGStrazzulloPNutiRMossettiG. SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone. J Bone Miner Res2010; 25:1375–84.
19.
RiminucciMRobeyPGSaggioIBiancoP. Skeletal progenitors and the GNAS gene: Fibrous dysplasia of bone read through stem cells. J Mol Endocrinol2010; 45:355–64.
20.
PiersantiSRemoliCSaggioIFunariAMichienziSSacchettiBRobeyPGRiminucciMBiancoP. Transfer, analysis, and reversion of the fibrous dysplasia cellular phenotype in human skeletal progenitors. J Bone Miner Res2010; 25:1103–16.
21.
CenniEFotiaCRustemiEYuasaKCaltavuturoGGiuntiABaldiniN. Idiopathic and secondary osteonecrosis of the femoral head show different thrombophilic changes and normal or higher levels of platelet growth factors. Acta Orthop2011; 82:42–9.
22.
FaviaGPilolliGPMaioranoE. Histologic and histomorphometric features of bisphosphonate-related osteonecrosis of the jaws: An analysis of 31 cases with confocal laser scanning microscopy. Bone2009; 45:406–13.
23.
RipamontiCIManiezzoMCampaTFagnoniEBrunelliCSaibeneGBareggiCAscaniLCislaghiE. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol2009; 20:137–45.
24.
GaspariniGSaponaroGDi NardoFMoroABonielloRCervelliDMarianettiTMPalazzoniGPeloS. Clinical experience with spiramycin in bisphosphonate-associated osteonecrosis of the jaw. Int J Immunopathol Pharmacol2010; 23:619–26.
25.
de NigrisFRossielloRSchianoCArraCWilliams-IgnarroSBarbieriALanzaABalestrieriAGiulianoMTIgnarroLJNapoliC. Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and CXCR4/angiogenesis and metastasis. Cancer Res2008; 68:1797–808.
26.
PerbalBZuntiniMZambelliDSerraMSciandraMCantianiLLucarelliEPicciPScotlandiK. Prognostic value of CCN3 in osteosarcoma. Clin Cancer Res2008; 14:701–9.
27.
ToffoliGBiasonPRussoADe MattiaECecchinEHattingerCMPaselloMAlberghiniMFerrariCScotlandiKPicciPSerraM. Effect of TP53 Arg72Pro and MDM2 SNP309 polymorphisms on the risk of high-grade osteosarcoma development and survival. Clin Cancer Res2009; 15:3550–6.
28.
PaselloMMichelacciFSciontiIHattingerCMZuntiniMCaccuriAMScotlandiKPicciPSerraM. Overcoming glutathione S-transferase P1-related cisplatin resistance in osteosarcoma. Cancer Res2008; 68:6661–8.
29.
HattingerCMStoicoGMichelacciFPaselloMSciontiIRemondiniDCastellaniGCFanelliMScotlandiKPicciPSerraM. Mechanisms of gene amplification and evidence of coamplification in drug-resistant human osteosarcoma cell lines. Genes Chromosomes Cancer2009; 48:289–309.
30.
SciontiIMichelacciFPaselloMHattingerCMAlberghiniMManaraMCBacciGFerrariSScotlandiKPicciPSerraM. Clinical impact of the methotrexate resistance-associated genes C-MYC and dihydrofolate reductase (DHFR) in high-grade osteosarcoma. Ann Oncol2008; 19:1500–8.
31.
ZuffaEManciniMBrusaGPagnottaEHattingerCMSerraMRemondiniDCastellaniGCorradoPBarbieriESantucciMA. P53 oncosuppressor influences selection of genomic imbalances in response to ionizing radiations in human osteosarcoma cell line SAOS-2. Int J Radiat Biol2008; 84:591–601.
32.
SpreaficoASchenoneSSerchiTOrlandiniMAngelucciAMagriniDBernardiniGCollodelGDi StefanoATintoriCBolognaMManettiFBottaMSantucciA. Antiproliferative and proapoptotic activities of new pyrazolo[3,4-d]pyrimidine derivative Src kinase inhibitors in human osteosarcoma cells. FASEB J2008; 22:1560–71.
33.
AvnetSSciaccaLSalernoMGancitanoGCassarinoMFLonghiAZakikhaniMCarboniJMGottardisMGiuntiAPollakMVigneriRBaldiniN. Insulin receptor isoform A and insulin-like growth factor II as additional treatment targets in human osteosarcoma. Cancer Res2009; 69: 2443–52.
34.
ManaraMCNicolettiGZambelliDVenturaSGuerzoniCLanduzziLLolliniPLMairaSMGarcia-EcheverriaCMercuriMPicciPScotlandiK. NVP-BEZ235 as a new therapeutic option for sarcomas. Clin Cancer Res2010; 16: 530–40.
35.
PignochinoYGrignaniGCavalloniGMottaMTapparoMBrunoSBottosAGammaitoniLMigliardiGCamussiGAlberghiniMTorchioBFerrariSBussolinoFFagioliFPicciPAgliettaM. Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways. Mol Cancer2009; 8:118.
36.
MirettiSRoatoITaulliRPonzettoCCilliMOliveroMDi RenzoMFGodioLAlbiniABuraccoPFerraciniR. A mouse model of pulmonary metastasis from spontaneous osteosarcoma monitored in vivo by Luciferase imaging. PloS One2008; 3:el828.
37.
De MariaRMirettiSIussichSOliveroMMorelloEBertottiAChristensenJGBiolattiBLevineRABuraccoPDi RenzoMF. Met oncogene activation qualifies spontaneous canine osteosarcoma as a suitable pre-clinical model of human osteosarcoma. J Pathol2009; 218:399–408.
38.
BergerMGrignaniGFerrariSBiasinEdel PreverA BrachAlibertiSSaglioFAgliettaMFagioliF. Phase 2 trial of two courses of cyclophosphamide and etoposide for relapsed high-risk osteosarcoma patients. Cancer2009; 115:2980–7.
39.
PicciPMercuriMFerrariSAlberghiniMBriccoliAFerrariCPignottiEBacciG. Survival in high-grade osteosarcoma: Improvement over 21 years at a single institution. Ann Oncol2010; 21:1366–73.
40.
BacciGRoccaMSaloneMBalladelliAFerrariSPalmeriniEForniCBriccoliA. High grade osteosarcoma of the extremities with lung metastases at presentation: Treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions. J Surg Oncol2008; 98:415–20.
41.
RossiGRimondiEBartalenaTGerardiAAlberghiniMStaalsELErraniCBianchiGToscanoAMercuriMVanelD. Selective arterial embolization of 36 aneurysmal bone cysts of the skeleton with N-2-butyl cyanoacrylate. Skeletal Radiol2010; 39:161–7.
42.
RocchiAManaraMCSciandraMZambelliDNardiFNicolettiGGarofaloCMeschiniSAstolfiAColomboMPLessnickSLPicciPScotlandiK. CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis. J Clin Invest2010; 120:668–80.
43.
ScotlandiKRemondiniDCastellaniGManaraMCNardiFCantianiLFrancesconiMMercuriMCaccuriAMSerraMKnuutilaSPicciP. Overcoming resistance to conventional drugs in Ewing sarcoma and identification of molecular predictors of outcome. J Clin Oncol2009; 27: 2209–16.
44.
GarofaloCManaraMCNicolettiGMarinoMTLolliniPLAstolfiAPandiniGLopez-GuerreroJASchaeferKLBelfioreAPicciPScotlandiK. Efficacy of and resistance to anti-IGF-lR therapies in Ewing's sarcoma is dependent on insulin receptor signaling. Oncogene. 2011 Jan 31. [Epub ahead of print]
45.
ZambelliDZuntiniMNardiFManaraMCSerraMLanduzziLLolliniPLFerrariSAlberghiniMLlombart-BoschAPiccoloEIacobelliSPicciPScotlandiK. Biological indicators of prognosis in Ewing's sarcoma: An emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP). Int J Cancer2010; 126:41–52.
46.
FerrariSHallK SundbyLukschRTienghiAWiebeTFagioliFAlvegardTADel PreverA BrachTamburiniAAlberghiniMGandolaLMercuriMCapannaRMapelliSPreteACarliMPicciPBarbieriEBacciGSmelandS. Nonmetastatic Ewing family tumors: High-dose chemotherapy with stem cell rescue in poor responder patients. Results of the Italian Sarcoma Group/Scandinavian Sarcoma Group III protocol. Ann Oncol2010 Nov 8. [Epub ahead of print]
47.
SalernoMAvnetSAlberghiniMGiuntiABaldiniN. Histogenetic characterization of giant cell tumor of bone. Clin Orthop Relat Res2008; 466:2081–91.
48.
PazzagliaLContiAChiechiANovelloCMagagnoliGAstolfiAPessionAKrenacsTAlberghiniMPicciPBenassiMS. Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases. Histopathology2010; 57: 59–72.
49.
ContiARodriguezGCChiechiABlazquezRMBarbadoVKrenacsTNovelloCPazzagliaLQuattriniIZanellaLPicciPDe AlavaEBenassiMS. Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis. Am J Pathol2011; 178: 88–97.
50.
RuggieriPMavrogenisAFUssiaGAngeliniAPapagelopoulosPJMercuriM. Recurrence after and complications associated with adjuvant treatments for sacral giant cell tumor. Clin Orthop Relat Res2010; 468: 2954–61.
51.
PrevidiSMaroniPMatteucciEBrogginiMBendinelliPDesiderioMA. Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and beta-catenin/Wnt pathways. Eur J Cancer2010; 46:1679–91.
52.
MarchiniCMontaniMKonstantinidouGOrrùRMannucciSRamadoriGGabrielliFBaruzziABertonGMerigoFFinSIezziMBisaroBSbarbatiAZeraniMGalièMAmiciA. Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies. PLoS One2010; 5:el4131.
53.
RucciNMillimaggiDMariMDel FattoreABolognaMTetiAAngelucciADoloV. Receptor activator of NF-kappaB ligand enhances breast cancer-induced osteolytic lesions through upregulation of extracellular matrix metalloproteinase inducer/CD147. Cancer Res2010; 70: 6150–60.
54.
FerlinAPepeAFacciolliAGianeselloLForestaC. Relaxin stimulates osteoclast differentiation and activation. Bone2010; 46:504–13.
55.
GranchiDBaglioSRAmatoIGiuntiABaldiniN. Paracrine inhibition of osteoblast differentiation induced by neuroblastoma cells. Int J Cancer2008; 123:1526–35.
56.
GranchiDCorriasMVGaraventaABaglioSRCangemiGCarliniBPaolucciPGiuntiABaldiniN. Neuroblastoma and bone metastases: Clinical significance and prognostic value of Dickkopf 1 plasma levels. Bone2011; 48:152–9.
57.
RoatoIGorassiniEBuffoniLLyberisPRuffiniEBonelloLBaldiICiuffredaLMussaAFerraciniR. Spontaneous osteoclastogenesis is a predictive factor for bone metastases from non-small cell lung cancer. Lung Cancer2008; 61:109–16.
58.
RoatoID'AmelioPGorassiniEGrimaldiABonelloLFioriCDelsedimeLTizzaniADe LiberoAIsaiaGFerraciniR. Osteoclasts are active in bone forming metastases of prostate cancer patients. PLoS One2008; 3: e3627.
59.
AmbrosiniVNanniCZompatoriMCampanaDTomassettiPCastellucciPAllegriVRubelloDMontiniGFranchiRFantiS. 68Ga-DOTA-NOC PET/CT in comparison with CT for the detection of bone metastases in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging2010; 37:722–7.
60.
CastellucciPFuccioCRubelloDSchiavinaRSantiINanniCAllegriVMontiniGCAmbrosiniVBoschiSMartoranaGMarzolaMCFantiS. Is there a role for 11C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml?Eur J Nucl Med Mol Imaging2011; 38:55–63.
61.
GasbarriniALiHCappuccioMMirabileLPaderniSTerziSBorianiS. Efficacy evaluation of a new treatment algorithm for spinal metastases. Spine (Phila Pa 1976)2010; 35:1466–70.
62.
PiccioliAMaccauroGRossiBScaramuzzoLFrenosFCapannaR. Surgical treatment of pathologic fractures of humerus. Injury2010; 41:1112–6.
63.
FiniMTschonMRonchettiMCavaniFBianchiGMercuriMAlberghiniMCadossiR. Ablation of bone cells by electroporation. J Bone Joint Surg Br2010; 92: 1614–20.
64.
MargiottaNOstuniRGandinVMarzanoCPiccinonnaSNatileG. Synthesis, characterization, and cytotoxicity of dinuclear platinum-bisphosphonate complexes to be used as prodrugs in the local treatment of bone tumours. Dalton Trans2009; (48): 10904–13.
65.
SalernoMCenniEFotiaCAvnetSGranchiDCastelliFMicieliDPignatelloRCapulliMRucciNAngelucciADel FattoreATetiAZiniNGiuntiABaldiniN. Bone-targeted doxorubicin-loaded nanoparticles as a tool for the treatment of skeletal metastases. Curr Cancer Drug Targets2010; 10:649–59.
66.
GrisendiGBussolariRCafarelliLPetakIRasiniVVeronesiEDe SantisGSpanoCTagliazzucchiMBarti-JuhaszHScarabelliLBambiFFrassoldatiARossiGCasaliCMorandiUHorwitzEMPaolucciPContePDominiciM. Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res2010; 70:3718–29.
67.
TirinoVDesiderioVd'AquinoRDe FrancescoFPirozziGGrazianoAGalderisiUCavaliereCDe RosaAPapaccioGGiordanoA. Detection and characterization of CD 133+ cancer stem cells in human solid tumours. PLoS One2008; 3:e3469.
68.
Di FioreRSantulliAFerranteRDGiulianoMDe BlasioAMessinaCPirozziGTirinoVTesoriereGVentoR. Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment. J Cell Physiol2009; 219:301–13.
69.
NeriSMarianiECattiniLFacchiniA. Long-term in vitro expansion of osteoarthritic human articular chondrocytes do not alter genetic stability: A microsatellite instability analysis. J Cell Physiol. 2010 Dec 28. [Epub ahead of print]
70.
GrigoloBLisignoliGDesandoGCavalloCMarconiETschonMGiavaresiGFiniMGiardinoRFacchiniA. Osteoarthritis treated with mesenchymal stem cells on hyaluronan-based scaffold in rabbit. Tissue Eng Part C Methods2009; 15:647–58.
71.
CavalloCDesandoGFacchiniAGrigoloB. Chondrocytes from patients with osteoarthritis express typical extracellular matrix molecules once grown onto a three-dimensional hyaluronan-based scaffold. J Biomed Mater Res A2010; 93:86–95.
72.
SpreaficoAChelliniFFredianiBBernardiniGNiccoliniSSerchiTCollodelGPaffettiAFossombroniVGaleazziMMarcolongoRSantucciA. Biochemical investigation of the effects of human platelet releasates on human articular chondrocytes. J Cell Biochem2009; 108: 1153–65.
73.
BendinelliPMatteucciEDogliottiGCorsiMMBanfiGMaroniPDesiderioMA. Molecular basis of antiinflammatory action of platelet-rich plasma on human chondrocytes: Mechanisms of NF-κB inhibition via HGF. J Cell Physiol. 2010;225(3):757–66.
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MarsichEBorgognaMDonatiIMozeticPStrandBLSalvadorSGVitturFPaolettiS. Alginate/lactose-modified chitosan hydrogels: A bioactive biomaterial for chondrocyte encapsulation. J Biomed Mater Res A2008; 84:364–76.
76.
KonEGobbiAFilardoGDelcoglianoMZaffagniniSMarcacciM. Arthroscopic second-generation autologous chondrocyte implantation compared with microfracture for chondral lesions of the knee: Prospective nonrandomized study at 5 years. Am J Sports Med2009; 37:33–41.
77.
GianniniSBattagliaMBudaRCavalloMRuffilliAVanniniF. Surgical treatment of osteochondral lesions of the talus by open-field autologous chondrocyte implantation: A 10-year follow-up clinical and magnetic resonance imaging T2-mapping evaluation. Am J Sports Med2009; 37Suppl 1:112S–8S.
78.
GianniniSBudaRVanniniFDi CaprioFGrigoloB. Arthroscopic autologous chondrocyte implantation in osteochondral lesions of the talus: Surgical technique and results. Am J Sports Med2008; 36:873–80.
79.
GianniniSBudaRVanniniFCavalloMGrigoloB. One-step bone marrow-derived cell transplantation in talar osteochondral lesions. Clin Orthop Relat Res2009; 467: 3307–20.
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De RosaATirinoVPainoFTartaglioneAMitsiadisTFekiAd'AquinoRLainoLColacurciNPapaccioG. Amniotic fluid-derived mesenchymal stem cells lead to bone differentiation when cocultured with dental pulp stem cells. Tissue Eng Part A2010 Nov 22. [Epub ahead of print]
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104.
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PanzavoltaSTorricelliPBracciBFiniMBigiA. Functionalization of biomimetic calcium phosphate bone cements with alendronate. J Inorg Biochem2010; 104: 1099–106.
106.
KonEDelcoglianoMFilardoGFiniMGiavaresiGFrancioliSMartinIPressatoDArcangeliEQuartoRSandriMMarcacciM. Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial. J Orthop Res2010; 28:116–24.
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