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The paper deals with a variant of Aucissa fibulae, specific for its decoration and quality of workmanship. These fibulae are ornamented with riveted animal figures. At present, four fibulae with the same characteristics can be distinguished, which we named the Otok variant after the find-spot of the most beautiful specimen. Three fibulae originate from Dalmatia, while one was discovered in Haltern, Germany. The paper discusses the dating and distribution frameworks, as well as the iconography of the Otok variant of Aucissa fibulae., U članku se obrađuje varijanta Aucissa fibula specifična po načinu ukrašavanja i kvaliteti izrade. Radi se o fibulama koje su ukrašene apliciranim životinjskim figurama. Trenutno se mogu izdvojiti četiri fibule istih značajki, koje smo prema nalazištu najljepšeg primjerka nazvali varijantom Otok. Tri su s dalmatinskog područja, a jedna je pronađena u Halternu u Njemačkoj. U članku se donose razmišljanja o datacijskim i distribucijskim okvirima te ikonografiji varijante Otok fibula tipa Aucissa.

Wiederholt wurde der Versuch unternommen, einen dauerhaften Aufenthalt des römischen Militärs im Illyricum bereits in spätrepublikanischer bzw. frühaugusteischer Zeit nachzuweisen. Dieser wurde mit dem Vorstoß des Caius Octavianus 35–33 vor Chr., dem bellum Pannonicum des Tiberius 12– 10 vor Chr., oder dem bellum Batonianum 6–9 nach Chr. in Zusammenhang gebracht. Trotz der Angaben in historischen Quellen war das römische Militär bis jetzt in Dalmatien erst seit der 1. Hälfte des 1. Jh. nach Chr. archäologisch klar zu fassen. Davon zeugen in erster Linie die Innschriften römischer Militäreinheiten. Kleinfunde sind zwar in wesentlich geringerem Maß veröffentlicht, doch Neufunde ändern zunehmend das Bild, das uns von den Innschriften vermittelt wird. So verfügen wir mittlerweile über Kleinfunde aus Tilurium und Sveta Trojica die mit dem Vorstoß des Caius Octavianus 35–33 vor Chr. In Zusammenhang gebracht werden können. Bei dieser Gelegenheit soll der Versuch unternommen werden, spätrepublikanische und augusteische Militaria in Burnum und Dalmatien zu identifizieren.

U knjizi su predstavljeni rezultati arheoloških iskopavanja i istraživanja legijskog logora Tilurija u Gardunu kod Trilja u razdoblju od 2007. do 2010. godine.

Wiederholt wurde der Versuch unternommen, einen dauerhaften Aufenthalt des römischen Militärs im Illyricum bereits in spätrepublikanischer bzw. frühaugusteischer Zeit nachzuweisen. Dieser wurde mit dem Vorstoß des Caius Octavianus 35–33 vor Chr., dem bellum Pannonicum des Tiberius 12–10 vor Chr., oder dem bellum Batonianum 6–9 nach Chr. in Zusammenhang gebracht. Trotz der Angaben in historischen Quellen war das römische Militär bis jetzt in Dalmatien erst seit der 1. Hälfte des 1. Jh. nach Chr. archäologisch klar zu fassen. Davon zeugen in erster Linie die Innschriften römischer Militäreinheiten. Kleinfunde sind zwar in wesentlich geringerem Maß veröffentlicht, doch haben sie bis jetzt das Bild bestätigt, das uns die Innschriften vermittelt haben. So verfügen wir aus der Zeit des bellum Batonianum über äußerst geringe Spuren des römischen Militärs in Pannonien, während sie in Dalmatien fast vollkommen ausbleiben. Anlässlich des 20sten Jubiläums der Grabungen im dalmatinischen Legionslager Tilurium soll der Versuch unternommen werden, spätrepublikanische und augusteische Militaria in Tilurium und Dalmatien zu identifizieren.

Prostor obrađen u okviru doktorskog rada obuhvaća međuriječje Krke i Cetine u razdoblju principata. Okosnicu rada čini tipološko-kronološka obrada rimske vojne opreme temeljem koje se dolazi do potvrde i dopune već poznatih činjenica izvedenih uglavnom iz povijesnih izvora i natpisa. Sustavnom obradom vojne opreme pojašnjavaju se međusobni odnosi vojnih i civilnih lokaliteta unutar regije, kao i odnos obrađene regije s ostalim dijelovima Rimskog Carstva. U radnji su obrađeni nalazi rimske vojne opreme prikupljeni iz više muzejskih institucija: Arheološki muzej u Splitu, Arheološki muzej u Zagrebu, Muzej cetinske krajine u Sinju i Muzej triljskog kraja u Trilju. Ukupno je obrađeno 486 predmeta, od čega je 46 određeno kao oružje, zaštitnoj opremi pripada 39 predmeta, a konjskoj 89. Najbrojnija je skupina osobne opreme sa 283 obrađena nalaza, a kao ostala oprema obrađeno ih je ukupno 29. U poglavlju Tipološko – kronološka analiza predmeti su obrađeni u tipološkim skupinama bez obzira na lokalitet s kojeg potječu, te je fokus na postavljanju, uz namjenske i tipološke i vremenskih okvira nalaza. U Zaključnim razmatranjima smo usporedili zastupljenost rimske vojne opreme na pojedinim nalazištima, te izdvojili datacijske okvire materijala obzirom na lokalitet nalaza. Od ukupnog broja od 486 nalaza čak 476 pronađeno je na području Tilurija i Salone, a na svim ostalim lokalitetima 9. Od tog je broja najveći broj nalaza, ukupno pet, iz Andetrija, dva su pronađena u Podgrađu kod Podstrane u Poljicima, a s po jednim nalazom zastupljeni su Balina glavica kod Umljanovića, Čaporice kod Trilja i Prugovo koje se nalazi na cestovnom pravcu od Klisa prema Muću. Usporedba nalaza iz Tilurija i Salone pokazala je na oba lokaliteta najbolju zastupljenost materijala iz razdoblja 1. st., no za razliku od gotovo potpunog izostanka nalaza 2. i 3. st. u Tiluriju, u Saloni je tako datiran materijal zastupljen u tek nešto manjem broju od onog iz 1. st. U Tiluriju su potvrđeni nalazi iz kasnorepublikanskog/ranoaugustovskog doba čime je po prvi put u sloju potvrđena ta faza logora. Materijal tog vremena nije zabilježen na području Salone. U Andetriju je oprema zastupljena s pet predmeta datiranima u vrijeme od 1. do 3. st., u Prugovu, Čaporicama i Balinoj glavici nalazi pripadaju 1. st. U Podgrađu su pojasna kopča i privjesak datirana u 1. st., s tim da privjesak pripada tipu kakvi se javljaju i početkom 2. st.

Introduction: Joint destruction in rheumatoid arthritis (RA) involves infiltration and activation of osteoclasts. Human osteoclast progenitors (OCPs) exhibit chemotaxis and synovial compartment in RA expresses different chemokines. We aimed to define chemotactic signals by analyzing expression of chemokine receptors on OCPs, chemokine levels and to assess differentiation potential of OCPs. Materials and methods: Mononuclear cells were separated from peripheral blood of healthy controls and RA patients. Phenotype of OCPs (CD3-CD19-CD56- CD11b+CD14+) was determined using flow cytometry for following chemokine receptors: CCR1, CCR2, CCR4, CXCR4. Chemokine ligand concentrations (CCL2, CCL3, CCL4, CCL5, CXCL9, CXCL10) were measured in serum and synovial fluid using flow cytometry bead based array. OCPs were sorted and cultured with M-CSF and RANKL. After two weeks, cells were stained for TRAP enzyme and positive, mature, osteoclasts were counted. Results: Human peripheral blood OCPs similarly expressed chemokine receptors CCR1, CCR2, CCR4 and CXCR4 in RA and healthy subjects. However, CCL2, CXCL9 and CXCL10 serum levels were higher in RA, while CCL4 and CXCL10 concentrations were significantly higher in synovial fluid compared to RA serum levels. Cell culture revealed no significant differences between RA and control group. Conclusions: Although differentiation potential and receptor expression of RA OCPs is similar to control, levels of several chemokines are upregulated, indicating a possible chemotactic mechanism of OCP migration to affected joints specifically associated with RA. In parallel, we are determining the cell population responsible for increased chemokine production, most probably of the monocyte/macrophage lineage, which is induced in RA by chronic inflammation.

Introduction. Rheumatoid arthritis (RA) is a chronic joint disease marked by persistent inflammation and osteodestruction. The mechanisms leading to joint destruction involve infiltration of osteoclasts, multinucleated cells derived from monocyte/macrophage lineage. Human osteoclast progenitors (OCPs) are contained among peripheral blood monocytes at low frequency even in healthy subjects. OCPs exhibit chemotaxis and, furthermore, synovial compartment of RA patients highly express different chemokines. The aim of our study was to define these chemotactic signals by analyzing expression of several chemokine receptors on OCPs in the peripheral blood, the levels of their respective ligands in serum and synovial fluid of RA patients and to assess differentiation potential of isolated OCPs. Methods. Mononuclear cells were separated from peripheral blood of healthy controls and RA patients. The phenotype of OCPs (CD3- CD19-CD56- CD11b+CD14+) was determined using flow cytometry for the following chemokine receptors: C5AR1, CCR1, CCR2, CCR4, CXCR4. Chemokine ligand concentrations (MIP-1α/CCL3, MIP-1β/CCL4, MCP- 1/CCL2, RANTES/CCL5) were measured in serum and synovial fluid of RA patients using flow cytometry bead based array. OCPs were sorted and cultured with M-CSF and RANKL. After two weeks, the cells were stained for TRAP enzyme and positive, mature, osteoclasts were counted. Results. Human peripheral blood OCPs similarly expressed chemokine receptors CCR1, CCR2, CCR4 and CXCR4 in RA and healthy subjects. However, MCP- 1/CCL2, MIP1a/CCL3 and MIP1b/CCL4 concentrations were significantly higher in synovial fluid, as well as CCL2 and CCL4 in serum. Cell culture revealed no significant differences in mature osteoclast count between RA and control group. Conclusions. Although OCPs in RA have a differentiation potential similar to controls, levels of several chemokines are upregulated, indicating a possible chemotactic mechanism of OCP migration to affected joints. These results may help to reveal a migration mechanism of OCPs specifically associated with RA in order to develop more efficient therapeutic approaches.

U knjizi su predstavljeni rezultati arheoloških iskopavanja i istraživanja legijskog logora Tilurija u Gardunu kod Trilja u razdoblju od 2002. do 2006. godine.

Introduction. Rheumatoid arthritis (RA) is chronic joint disease marked by the persistent inflammation and osteodestruction, causing progressive disability and crippling. The mechanisms leading to joint destruction involve infiltration of inflammatory cells and T lymphocytes as well as activation of osteoclasts, multinucleated cells derived from monocyte/macrophage lineage. Human osteoclast progenitors (OCPs) are contained among peripheral blood monocytes and have been shown to be present at low frequency in healthy subjects. The accumulation of T lymphocytes and inflammatory cells at the site of inflammation involves, among others, chemokine signals. It is known that synovial tissue and synovial fluid from RA patients highly express several chemokines and, furthermore, that OCPs exhibit chemotaxis as well. The aim of our study was to define these chemotactic signals by analyzing expression of several chemokine and chemokine receptors on T lymphocytes and OCPs in the peripheral blood of RA patients. Methods. Mononuclear cells were isolated from peripheral blood of healthy controls and RA patients, after obtaining approval from the Ethical Committee and informed consent from patients. The phenotype of isolated mononuclear cells was determined using flow cytometry. Expression of following chemokine receptors was analyzed on OCPs (CD3-CD19-CD56-CD11b+CD14+): C5AR1, CCR1, CCR2, CCR4, CXCR4. T lymphocytes (CD3+/CD4+ or CD3+/CD8+) were analyzed for expression of CXCR5, CCR4, CCR6 chemokine receptors. Lymphoid lineage positive (CD3+/CD19+/CD56+) population was then sorted and analyzed for the expression of the respective chemokine ligands: SDF-1/CXCL12, MIP-1α/CCL3, MIP- 1β/CCL4 and MCP-1/CCL2 by qPCR. Results. We have verified that human peripheral blood OCPs differently express chemokine receptors CCR1, CCR2, CCR4 and CXCR4. Expression of CCR4 and CXCR4 was found on approximately 10-15% of OCPs, with no difference between RA and control subjects. A small subpopulation of OCPs expressing CCR1 (under 1%) was expanded in RA patients compared to controls, whereas the proportion of CCR2+ OCPs was two-fold lower in RA patients (approximately 10%). The proportion of T lymphocytes expressing CCR4 was two-fold higher in RA patients compared to controls. T lymphocyte expression of CXCR5 and CCR6 was similar between RA and control group. Chemokine gene expression of sorted lymphoid lineage positive population from RA patients revealed two-fold higher expression of MCP-1/CCL2 compared to controls. Conclusions. Expression of several chemokine receptors is altered in RA on both OCPs and T lymphocytes, and T lymphocytes themselves exhibit altered expression of CCL2 indicating a possible specific chemotactic mechanism and environment in RA. These results may help to reveal migration mechanism of T lymphocytes and OCPs specifically associated with RA in order to develop more efficient therapeutic approaches.

BACKGROUND: Fas/Fas ligand (FasL) apoptotic pathway in hepatocytes is thought to be involved in the pathogenesis of liver disease such as viral hepatitis and nonalcoholic steatohepatitis. Although it is known that various immune mediators modulate hepatocyte susceptibility to Fas/FasL- mediated apoptosis, the exact effects of pro- inflammatory cytokines on the apoptotic processes in hepatocyte are still not well understood. In our study we aimed to investigate the effect of acute inflammatory response on Fas/FasL-mediated hepatocyte apoptosis using a model of lipopolysaccharide (LPS)-induced acute inflammation. METHODS: Acute inflammation was induced in male C57BL/6 mice by intraperitoneal injection of LPS (0.1 µg/g body weight in 10 µL/g body weight of sterile saline) while the control group of animals received the same volume of sterile saline. After 2.5 hours both groups were treated with anti-Fas activating antibody (0.1 μg/g body weight, intravenously) in order to induce hepatocyte apoptosis. Mice were sacrificed after additional 6 hours and plasma (ALT, AST) and liver tissue (pathohistology, caspase activity assays, qPCR) were collected for the analyses. RESULTS: Mice pre-treted with LPS had lower levels of ALT (32 ± 11 vs 164 ± 61 U/L, p

Introduction: Various proinflammatory mediators have been shown to affect bone metabolism by modulating the activity and functional interactions of principal bone cells, bone forming osteoblasts and bone resorbing osteoclasts. Pentraxin 3 (PTX3) is a highly conserved member of the long pentraxins subfamily produced by somatic and immune cells in response to proinflammatory stimuli. Its biological roles have been described in various conditions, such as infections, female fertility and angiogenesis. We aimed to elucidate the role of PTX3 in physiological bone formation as well as in the process of fracture healing. Methods: Wild type (WT) mice and mice deficient for the PTX3 gene (PTX3-KO) (both genders, 8-weeks of age) on C57BL/6 background were used, after obtaining the approval from the Ethical committee. Cells from bone marrow, homogenized bone shafts and spleen were harvested and cultured to stimulate differentiation into osteoblast (by the addition of ascorbic acid 50 μg/ml, 10−8 M dexamethasone, and 8 mM β-glycerophosphate) or osteoclast lineage (by the addition of RANKL (40 ng/mL) and M-CSF (15 ng/mL)). Same populations were analyzed by flow-cytometry to assess the proportion of putative osteoclast and osteoblast progenitor cells. Bone metabolism in vivo was determined by histomorphometry and micro- computerized tomography (μCT) using standard structural bone parameters (trabecular volume (BV/TV), trabecular thickness, trabecular number and trabecular separation) and dynamic parameters of bone formation rate. Fracture model was introduced to further investigate the importance of PTX3 in bone healing process. The method of Bonnarens and Einhorn was modified to produce standardized closed tibial fracture in WT and PTX3-KO female mice after insertion of stainless steel pin into the tibial medullary cavity for bone fragment fixation. Mice were sacrificed three weeks post-fracture, and the quality and composition of callus tissue were assessed by μCT. Results: PTX3-KO mice had lower bone mass (BV/TV 2.72 ± 1.23 for females and 5.39 ± 1.73 for males) than their WT littermates (BV/TV 5.03 ± 0.87 for females and 7.04 ± 0.87 for males, p

The featured items of a military nature: weapons, protective equipment, pieces of military clothing and horse gear ; mostly belong to the time of the 1st century, which is to be expected when taking into account that it is in this camp that the VII Legion resided – more specifically, most of the camps residents at this time were soldiers. After the departure of the VII Legion in the middle of the 1st century, the camp retained a significant military garrison until the middle of the 3rd century. As evidenced by found inscriptions, Gardun was also a beneficiary station. Late Antique materials, represented to a significantly lesser extent, confirms the already known fact that in Gardun life continued throughout the Late Antique period, when it was most probably used as a fort for defensive purposes. The offensive equipment preserved includes arrows and spears, ballistic projectiles, parts of swords and a dagger. military equipment also consisted of equipment for the protection of soldiers in battle. Among the findings from Gardun, in this group belong parts of helmets, shields and armor. Horse pendants are the most numerous findings of horse equipment in Roman military localities. The earliest pendants appear from the age of Augustus, and last through the 2nd century. From the second half of the 2nd century pendants fall out of fashion.An indispensible find at the military camp was the pickax (dolabra), a tool which is found almost exclusively in a military context. Three belt buckles with mounts, two belt tangs, as well as a spear and arrowhead, belong to the Late Antique period. The buckles belong to the period of the second half of the 4th and 5th centuries. Amphora shaped strap ends, such as those found in Gardun, are numerous on the territory of the entire Roman Empire, and they made up part of the “belt set” of military belts in the time of Dominate. On the basis of their typology, they are dated to the 4th century.

U radu su analizirani prikazi oružja na spomenicima iz Tilurija i na spomenicima koji se mogu povezati s radionicum u Tiluriju.

The largest and most important city in the Roman province of Dalmatia was Salona. As the provincial economic and administrative hub from the Early Roman period until the Byzantine era, the city of Salona was primarily a civilian settlement, but the military presence has been recorded in numerous inscriptions commissioned by veterans and soldiers, legionary and auxiliary troops stationed in the province, or soldiers who were assigned to the staff of the consul. Besides the data derived from written sources and numerous epigraphic inscriptions, the military presence in Salona is also demonstrated by in the finds of military gear, which is generally held in the Archaeological Museum in Split. First-century components of gear used by Roman soldiers, riding harnesses and weapons from Salona was published in the article.

Grave monuments held in the Archaeological Museum in Split containing depictions of portions of Roman military gear are analyzed in this work. The motifs on the stelae are diverse: weapons, implements, designations of military status, clothing and accoutrements, musical instruments. Most of the stelae are architectural stelae. The most numerous date to the first century. The portrayals on them do not differ greatly from the gear shown on stelae in other parts of the Empire. The stelae belonging to members of the cohors II Cyrenaica are specific in that they bear detailed portrayals of archery gear. Military grave stelae had appeared since the Late Republic era, and most date to the first century and during that time they spread from Italy to the Roman provinces together with the expansion of the Roman Empire’s territory. During the second century, their numbers declined, but they appeared over a very wide territory. For the purposes of this study, it is significant that the decline in their quantity was paralleled by a decline in quality, with less attention dedicated to details. In the third century their number increased in some territories of the Empire, and they were also present in larger urban centres. Stelae as military grave monuments were used by soldiers until the fourth century, and thereafter they fell out of use. This was also the situation in the province of Dalmatia, where the most numerous and highest quality military stelae were made in the first century. The highest number of military units were posted in Dalmatia during this period. Production of grave monuments proceeded in both legionary camps during this period, Tilurium (Legio VII Claudia Pia Fidelis) and Burnum (Legio XI Claudia Pia Fidelis). Most of the stelae examined herein, eight in all, were discovered in Roman-era Salona, while four are from Tilurium, three from Dugopolje, two from Andetrium, and one is from Narona. Generally they can be dated to the first century, while a smaller number of stelae date to the second and third centuries. Military gear is a very broad concept, and besides assault and defensive weaponry, it also includes implements which soldiers had to carry with them, clothing and footwear, riding gear, insignia, honours and medals, meaning everything which denoted a soldier as such and all of the equipment he used.

Osteoclasts play a pivotal role in excessive bone destruction of arthritic joints. Many cytokines are involved in the pathogenesis of arthritis, acting as osteoclastogenic factors, but their effects are not fully revealed. Our aim was to compare the expression profile of selected proinflammatory factors and osteoclastogenic potential of peripheral-blood mononuclear cells (PBMC) between control subjects and arthritic patients (including rheumatoid arthritis (RA) and spondyloarthritis (SpA)). In addition, we assessed osteoclastogenic potential of PBMC and local synovial-fluid derived mononuclear cells (SFMC) in patients with RA and SpA. PBMC were collected from control subjects (n=12), whereas PBMC and SFMC were collected from RA patients (n=10) and SpA patients (n=15), either with ankylosing spondylitis (AS=5) or psoriatic arthritis (PsA=10), after the informed consent. Osteoclasts were stimulated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and detected as tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells. RNA was extracted from PBMC/SFMC cells, reversely transcribed to cDNA, and amplified by quantitative PCR for the expression of osteoclast differentiation genes (RANK, cFms, TRAP) and inflammatory mediators (CCL2, VEGF, IL-17, IL-18, TNF-, and FasL). In addition, serum and synovial fluid levels of the same mediators were determined by ELISA. Serum levels of inflammatory mediators CCL2, IL-17 and IL-18 were higher in arthritic patients compared with control subjects, whereas synovial fluid levels of CCL2, VEGF, TNF- and IL- 18 were higher in RA compared with other patient groups. In addition, gene expression of inflammatory mediators CCL2, IL-17 and IL18 were higher in PBMC and SFMC of arthritic patients compared with control subjects. In vitro osteoclastogenesis showed higher osteoclastogenic potential for PBMC but similar for SFMC in RA compared with AS and PsA patients. In parallel, gene expression of osteoclast differentiation genes RANK and TRAP was higher in osteoclastogenic cultures derived from PBMC of RA patients. Our results indicate that patients with RA have greater osteoclastogenic potential compared with control subjects and SpA patients, which is paralleled with the increased expression of proinflammatory mediators. These findings may be relevant for the development of therapeutic approaches aimed to modulate proinflammatory as well as osteoclastogenic effects of those factors.

Within the bone marrow microenvironment mesenchymal and hematopoietic cells are anatomically and functionally related. In our previous study we hypothesize that cells expressing smooth muscle a-actin promoter (aSMA) directed transgene represent mesenchymal progenitors of adult bone tissue and confirmed that aSMA+ cells have the potential for terminal differentiation into mature osteoblast lineage cells in vitro and in vivo. We now proposed that aSMA+ cells also comprise hematopoietic progenitors that may differentiate toward hematopoietic lineages. This is in line with recent studies that identified progenitor cells expressing both mesenchymal and hematopoietic markers, challenging the long-existing postulation of early separation between those two lineages. In order to trace phenotypic and functional characteristics of aSMA+ cells, we generated aSMACreERT2 transgenic mice and we characterized its expression by crossing it with the Ai9 reporter transgenic line to generate aSMACreERT2/Ai9 (SMA9) mice. In a time-course of in vivo tamoxifen induction we were able to identify aSMA+ cells within the bone marrow compartment, comprising less than 0.1% of bone marrow cells 4 days after the first injection and reaching approximately 0.3% among bone marrow cells 65 days after the first tamoxifen injection. Flow-cytometric analysis confirmed that majority of cells express CD45 together with other hematopietic lineage markers, such as CD11b, Gr-1, Ter119, B220 or CD3. However, around 10% of cells were CD45+ but negative for all other lineage markers. Three weeks (19 days) after the first tamoxifen injection those cells expressed immature markers Sca-1 and CD34, but were negative for endothelial markers CD106 and CD31. Supposedly, those cells generate mature hematopoietic cells that are released into circulation, since we found around 0.15% aSMA+ cells in the peripheral blood, all expressing hematopoitic markers. Moreover, sorted aSMA+ cells gave rise to myeloid/monocyte colonies in the methylcellulose cultures. In the parabiotic pairs between the wild-type and transgenic SMA9 mouse, we could detect aSMA+ cells in circulation as well as rare aSMA+ cells within the spleen of the wild-type counterpart. On the other hand, CD45- bone marrow population expressed mesenchymal markers such as PDGFb and leptin receptor and increased in the percentage with the time after tamoxifen induction. Interestingly, certain percentage of CD45low cells also expressed mesenchymal markers together with Sca-1. Our findings provide evidence of the potency of aSMA+ population to give rise to mature mesenchymal as well as hematopietic cells. In further experiments we aimed to identify intracellular signaling molecules that control the bifurcation between progenitor commitments to those lineages.

Background/aim. Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS). Some studies suggested that high mobility group box 1 (HMGB1) has a role in amplifying neuroinflammatory processes in MS. Our study aimed to assess changes in HMGB1 and its receptor for advanced glycation end products (RAGE) in peripheral blood (PB) and cerebrospinal fluid (CSF) of MS patients. Methods. PB and CSF were collected from healthy controls (Ctrl ; n=16, age range 26-60) and MS patients (n=22, age range 20-48) after the informed consent. Control patients were routinely undergoing epidural anesthesia prior to lower extremity surgery, allowing obtainment of CSF. Soluble RAGE (sRAGE) and HMGB1 were measured in CSF and plasma by ELISA. Gene expression (as RNA relative quantity) in PB mononuclear cells (PBMC) was detected by qPCR for RAGE, HMGB1 and several proinflammatory cytokines. Results are expressed as median (range). Results. ELISA showed lower CSF sRAGE in MS (2.68 (0-13.45) pg/mL in MS vs. 9.08 (3.35-16.15) pg/mL in Ctrl, p=0.02). Gene expression in PBMC revealed no difference between group for IL- 1β, TNF-α, IL-6 and RAGE, only IL-1α was increased (1.55 (0.83- 309.48) in MS vs. 1.02 (0.22-3.75) in Ctrl ; p=0.05), whereas HBGB1 was decreased in MS (1.95 (0.53-3.14) in MS vs. 2.54 (0.79-5.41) in Ctrl ; p=0.04). Conslusions. Lower level of decoy sRAGE in CSF may allow enhanced HMGB1 proinflammatory effects within CNS. IL-1α is possible upstream mediator of HMGB1 release, whereas downregulated HMGB1 expression in PBMC may represent the compensatory mechanism to reduce inflammatory process.

Background: Multiple myeloma (MM) is B-lymphocyte neoplasia, characterized by the slow proliferation of malignant plasma cells in the bone-marrow (BM). Multiple anti-apoptotic signaling mechanisms contribute to the accumulation of myeloma cells within the BM and account for their resistance to chemotherapy. Therefore, investigation of the effects of different agents on the balance between pro- and anti-apoptotic factors in the malignant clone would contribute to the development of novel therapeutic strategies in MM. Aim: We determined the effects of several currently used anti-myeloma agents and their possible additive action on the inhibition of proliferation and enhancement of apoptosis of different human myeloma cell lines. Material and methods: Human myeloma cell lines NCI-H929, RPMI 8226 and JJN3 (ADCC-LGC and DSMZ cell line collection) and Theil (a gift from Dr. K. Pulford, University of Oxford, UK) were treated with bortezomib (Millenium Pharmaceuticals), dexamethasone, cyclosporine and thalidomide (Sigma-Aldrich) for 48 hrs. Cell line proliferation was assessed by the colorimetric MTT assay, whereas viability and apoptosis were evaluated by annexin V/propidium iodide staining. Gene expression of pro-apoptotic (Bax and p21) and pro-survival molecules (Bcl-2 and c-Myc) was assessed by real-time AB7500 instrument (Applied Biosystems). Additionally, we assessed the expression of SPARC (secreted protein acidic and rich in cysteine), involved in the cell de-adhesion from BM matrix and tumor pathogenesis. Results: Anti-myeloma agents (dexamethasone, bortezomib and thalidomide) achieve their effects by different cellular mechanisms. In addition, cyclosporine was included for its ability to increase cell sensitivity to other cytostatics. Each cell line, representing different biological variant of MM, has shown unique pattern of the expression of pro- and anti-apoptotic genes and, in addition, responded differently to anti-myeloma treatment. The most potent additive effect of drug combinations, including thalidomide/bortezomib, thalidomide/cyclosporine and bortezomib/cyclosporine, was noticed on the cellular and molecular level, as suppressed proliferation and shift in the balance of pro- and anti-apoptotic genes. Conclusion: Resistance to apoptosis, common in myeloma cells, depends on the constitutive expression of molecules acting at cell-cycle checkpoints and activated intracellular pathways in the particular circumstances. We observed that the susceptibility of myeloma cells to specific treatment is determined by their intrinsic balance between pro-survival and pro-apoptotic factors. Certain drug combinations, specifically thalidomide or bortezomib with cyclosporine, decreased Bcl-2/Bax ratio, a key indicator of enhanced apoptosis. Our findings suggest that the insight into the molecular events in the affected clone could enable administration of a specific individualized therapy which would be more effective in eradicating the malignant clone.

Cardiac myxoma (CM) represents the most prevalent type of primary cardiac tumors in adults, constituting up to 50-85% of all benign lesions of the heart. Due to their strategic localization and inherent pathohistological characteristics, they are considered as quite malignant entities with very serious consequences for morbidity and mortality of affected patients. Surgical resection of cardiac myxoma is currently the only treatment of choice. The purpose of this study was to determine the expression pattern of pannexin family (Panx 1/2/3) of gap junction proteins in sporadic cardiac myxoma cases. A total of 28 consecutive patients with sporadic cardiac myxoma diagnosed from 2002 to 2010 at Department of Cardiac Surgery, University Hospital Centre Zagreb were included in the study. Tumour tissue sections obtained from archival FFPE tumor tissue blocks (n=25) or fresh surgical tissue samples (n=3) snap-frozen in liquid N2 were used for immunohistological staining and RNA isolation. Immunohistochemical staining was performed with rabbit polyclonal anti-human pannexin-1, 2 and 3 antibody (AbCam ab78380, ab55917, ab98093) using DAB substrate and HRP reaction. RNA isolation, in vitro transcription and qRT-PCR were performed using TRI Reagent and RNeasy Mini kit, gene specific Quanti Tect Primer Assay and 7500 qRT-PCR system. Obtained results showed positive expression pattern for Panx 1- 3 in tumor cells (lepidic tumor cells arranged singly or in small clusters and vasiforme cell aggregations) of all analyzed samples on protein and mRNA level. The significance, of pannexin gene expression as a marker for cardiac myxoma has still to be elucidated.

Lipopolysaccharide (LPS), the major component of the outer membrane of gram-negative bacteria, has long been recognized as an important factor in promoting chronic inflammation and is involved in the pathogenesis of inflammation- and infection-induced bone diseases. Although it is known that LPS induces several pro-inflammatory molecules that can enhance bone resorption, and has a direct effect both on osteoclasts and on osteoblasts, the underlying mechanisms of action have not been fully defined. The aim of this study was to clarify the direct effect of LPS on in vitro differentiation of bone cells, osteoclasts and osteoblasts, depending on the dose of LPS and the bone cell differentiation stage at the time of LPS treatment. Osteoclasts were differentiated from bone marrow cells by the addition of RANKL (receptor activator of NF-B ligand) and M-CSF (monocyte/macrophage colony-stimulating factor) ; whereas osteoblasts were differentiated from bone marrow cells by the addition of ascorbic acid, dexamethasone and β-glycerophosphate. Several doses of LPS have been added to osteoblastogenic and osteoclastogenic cultures at various cultivation time-points. Osteoclasts were significantly more sensitive to LPS treatment, showing a detectable response at the very low dose of 0.005 g/mL, whereas osteoblasts showed a detectable response starting with a dose of 2 g/mL. Furthermore, a low dose of 0.025 g/mL LPS completely inhibited osteoclast differentiation, whereas a dose of 10 g/mL only partially suppressed osteoblast differentiation. Results for the time-response experiments, depending on the bone cell differentiation stage at the time of LPS treatment, showed significant inhibition of osteoclastogenesis with LPS added at the culture start-point, but stimulation of osteoclastogenesis when applied on the RANKL-primed commited preosteoclasts. In osteoblastogenis cultures, the direct LPS effect was exclusively inhibitory, but inhibition intensity depended on the time-point and duration of LPS treatment ; the LPS suppressive effect was weaker if applied on the commited preosteoblasts. Activity of the differentiation enzymes, tartarate resistant acid phosphatase (TRAP) for osteoclasts and alkaline phosphatase (AP) for osteoblasts, confirmed the results of the counts of differentiated bone cells. Differentiation gene expression pattern mirrored the dose- and time-response effect of LPS on the number of differentiated bone cells. Expressions of all analyzed osteoclast (RANK, calcitonin receptor, cFms and cFos) and osteoblast (AP, osteocalcin, Runx2, RANKL and osteoprotegerin) differentiation genes were suppressed by LPS during bone cell differentiation. RANKL was the only exception, showing an increase in the expression by LPS. We can conclude that LPS increases bone cell resorption potential by stimulating differentiation and activity of RANKL-primed osteoclasts, and increasing osteoblastic RANKL expression paralleled by suppressed osteoblast differentiation.

Breast cancer (BC) is the most prevailing malignancy among worldwide female population, with constantly increasing incidence and serious consequences on morbidity and mortality of affected patients. Genotypically and phenotypically BCs represent very heterogeneous group of tumours, diverse in their pathohistological features, expression of molecular markers, malignant/metastatic potential, clinical presentation, prognosis, and response to therapy. The purpose of this preliminary study was to determine the expression pattern of pannexin family (Panx 1/2/3) of gap junction proteins in invasive ductal breast carcinoma. A total of 27 female patients with diagnosed invasive ductal BC were included in the study. All cases were graded according to the modified criteria of Scarff Bloom-Richardson, as described by Elston and Ellis. Tumour tissue samples surgically removed from each patient (primary tumor and positive axillary lymph nodes) were embedded in paraffin blocks for immunohistological staining or snap- frozen in liquid N2 for RNA isolation. Immunohistochemical staining was performed with rabbit polyclonal anti-human pannexin-1, 2 and 3 antibody (AbCam ab78380, ab55917, ab98093) using DAB substrate and HRP reaction. RNA isolation, in vitro transcription and qRT-PCR were performed using TRI Reagent and RNeasy Mini kit, gene specific Quanti Tect Primer Assay (Qiagen) and 7500 qRT-PCR system (Applied Biosystem). Obtained results showed positive (protein, mRNA) expression pattern ranging from diffuse (Panx2) to granular (Panx1, Panx3) cytoplasmatic staining with slight or no membrane positivity in tumor cells of all analyzed samples. However, the significance, if any, of their expression for tumorigenesis of invasive ductal breast carcinoma has still to be elucidated.

U članku su obrađene fibule iz vojnog logora Tilurij, a čuvaju se u Muzeju Cetinske krajine u Sinju i u Arheološkom muzeju u Splitu. Zastupljeno je deset tipova fibula, a jednak broj otpada na vojničke (aucissa, snažno profilirane fibule, koljenaste, omega, lukovičaste) i one koji se uglavnom pripisuju civilnoj nošnji (višestruko raščlanjene, lučna fibula s dvije igle, domaća varijanta rane zglobne fibule, sidrasta, te fibula s podvijenom nogom). Bitna se razlika uočava u brojčanoj zastupljenosti: fibule civilne nošnje su malobrojne (dvije višestruko raščlanjene, po jedna od ostalih tipova), a puno su bolje zastupljene vojničke (aucissa: četrnaest s natpisom, osamnaest bez natpisa, pet snažno profiliranih, dvije koljenaste, dvije omega i tri lukovičaste fibule). Uočljiva je i razlika u zastupljenosti ranijih i kasnijih tipova. Najbrojnije su fibule ranijeg razdoblja, odnosno iz vremena dok je logor bio legijski, dok su kasniji tipovi znatno slabije zastupljeni.

The largest and most important city in the Roman province of Dalmatia was Salona. As the provincial economic and administrative hub from the Early Roman period until the Byzantine era, the city of Salona was primarily a civilian settlement, but the military presence has been recorded in numerous inscriptions commissioned by veterans and soldiers, legionary and auxiliary troops stationed in the province, or soldiers who were assigned to the staff of the consul. Besides the data derived from written sources and numerous epigraphic inscriptions, the military presence in Salona is also demonstrated by in the finds of military gear, which is generally held in the Archaeological Museum in Split. Components of gear used by Roman soldiers, riding harnesses and weapons from Salona have been dated from the Early Imperial period to Late Antiquity.

Prikaz međunarodnog skupa o rimskoj vojnoj opremi - XVII Romec, održanog u Zagrebu od 24. do 27. svibnja u Zagrebu.

Breast cancer is the most prevailing malignancy among worldwide female population, with constantly increasing incidence and serious consequences on morbidity and mortality of affected patients. It represents genotypically and phenotypically very heterogeneous group of tumors that are diverse in their pathohistological features, expression of molecular markers, malignant/metastatic potential, clinical presentation, prognosis, and response to therapy. The purpose of this preliminary study is to determine the expression pattern of pannexin family (Panx 1, 2 and 3) of gap junction proteins in invasive ductal breast cancer in female patients. So far a total of 27 patients with invasive ductal breast cancer (diagnosed during the 2010 in Department of Pathology, University Hospital for Tumors, University Hospital “Sestre milosrdnice”, Ilica 197, Zagreb, Croatia) were included in this study. Immunohistochemical staining for pannexin 1 and 2 was performed with rabbit polyclonal anti-human pannexin-1 and pannexin-2 antibody (AbCam ab78380, AbCam ab55917) using DAB substrate and HRP reaction. Results obtained so far showed positive expression pattern for pannexin 1 and 2, both on a protein and mRNA level (data not shown). Immunohistological staining for pannexin 1 showed diffuse and granular cytoplasmatic staining with slight positivity of cell membranes in all analyzed samples while Pannexin 2 showed only diffuse cytoplasmatic staining without membrane involvement.

Aus Tilurium und seiner unmittelbaren Umgebung stammt eine ganze Reihe von Steindenkmälern die sich durch Waffendarstellungen auszeichnen. Diese Denkmäler lassen sich in zwei Gruppen gliedern. Zur ersten Gruppe sind die Grabstelen aus Tilurium zusammengefasst, während das Tropaeum aus Tilurium als einzigartiges Steindenkmal zu einer eigenständigen Gruppe zu zählen ist. Das Tropaeum aus Tilurium Als bekanntestes und bedeutendstes Denkmal mit Waffendarstellungen ist das Tropaeum aus Tilurium zu nennen. Erhalten sind nur zwei Fragmente. Beim ersten handelt es sich um die vollkommen erhaltene äußerste rechte Platte der Vorderfront (Arheološki Muzej – Split, Inv. Nr. D 129) und beim zweiten um das Fragment der äußersten linken Platte der Vorderfront (Muzej Cetinske krajine, Inv. Br 381). Aufgrund der beiden Fragmente konnte Cambi die Vorderfront rekonstruieren und auch eine Rekonstruktion des gesamten Denkmals vorgeschlagen. An der Vorderfront befand sich ein Innschriftfeld in Form einer Tabula ansata. Links und rechts war je ein Wie üblich besteht dieses aus einem Pfahl an dem eine Rüstung, Schilde, Lanzen usw. aufgehängt sind. Ans Tropaeum sind weiters zwei besiegte Barbaren gekettet, die unterschiedliche Tracht tragen. Unterhalb des Inschriftfeldes war ein Waffenfries dargestellt der aus Rüstungen und Schilden besteht. Auf den Seiten des Denkmals dürfte ein Bukranien-Girlanden Fries dargestellt gewesen sein. Das gesamte Denkmal konnte ursprünglich ca. 8, 20-8, 40 x 7, 30-7, 60 m (bzw. 28x25 Fuß) gewesen sein. Stilistische Merkmale, der Fundort und die bekannten historischen Ereignisse lassen darauf schließen, dass das Tropaeum die Niederschlagung des Aufstands der panonisch - dalmatinischen Völker zwischen 6 und 9 nach Chr. feierte. Es durfte also im 2. Jahrzehnt des 1. nachchristlichen Jahrhunderts errichtet worden sein. Die Grabstelen aus Tilurium Bei den übrigen Denkmälern handelt es sich um Grabstelen römischer Soldaten die zum Großteil in der VII. Legion, bzw. in verschiedenen in Tilurium stationierten Kohorten, gedient haben. Es hat bereits H. Hofmann auf einige Grabdenkmäler aus Tilurium aufmerksam gemacht und diese zum Typ der ‚kleinasiatischen Grabfassade‘ zusammengefasst. Dieser Grabsteintyp ist aber nicht nur für Tilurium typisch. Seit Hofmann ihn zum ersten Mal zusammengestellt hat, werden zunehmend auch in anderen Orten in der römischen Provinz Dalmatien vergleichbare Funde registriert. So in der Provinzhauptstadt Salona, in der Umgebung des Kastells Bigeste und in Norddalmatien. Diese Grabstelen werden allgemein einer Werkstätte in Tilurium zugeschrieben. Die Grabstelen zeichnen sich durch einen architektonischen Aufbau aus, der eine monumentale Grabarchitektur, einen Naiskos bzw. eine Aedicula imitiert und Türdarstellungen enthält. Ein weiteres Kennzeichen sind oft wiederkehrende Waffendarstellungen die verschiedene Teile dieser Grabstelen dekorieren. Sehr beliebt ist ein Waffenfries der zum Aufbau der Aedicula gehört. Weitere Waffendarstellungen lassen sich als Selbstdarstellungen der Verstorbenen deuten und sind innerhalb der Aedicula oder am unteren Teil der Grabstelen angebracht. Beide Arten von Waffendarstellungen sind auch auf reduzierten Formen dieses Grabsteintyps anzutreffen. Der Waffenfries Der Waffenfries ist als dekoratives Element logischer Bestandteil einer Aedicula und eines Soldatengrabsteines. In Tilurium ist er auf mehreren Grabstelen der VII. Legion verzeichnet (Arheološki muzej – Split, Inv. Nr. 2588 A). Ein Waffenfries tritt auch auf vergleichbaren Grabstelen der VII. Legion auf, die von anderen Werkstätten nach dem Muster aus Tilurium errichtet worden dürften – so in der Provinzhauptstadt Salona und in der Umgebung des Kastells Bigeste. Die Selbstdarstellungen der Verstorbenen Andere Waffendarstellungen und Darstellungen militärischer Gegenstände die ebenfalls auf Grabstelen römischer Soldaten in Tilurium verzeichnet sind lassen sich als Selbstdarstellungen der Verstorbenen deuten. Diese nehmen meistens den unteren Teil der Grabstelen ein und lassen den Verstorbenen als Angehörigen einer bestimmten Truppe erkennen was bei Angehörigen der Cohors II Cyrrhestarum belegt ist. Bei einer Grabstele aus Tilurium kann man den Verstorbenen aufgrund der Werkzeugdarstellungen als immunes, genauer als Steinmetz (lapidarius) deuten (Arheološki muzej – Split, Inv. Nr. 1982). Das schönste Beispiel ist eine Grabstele mit Darstellung von militärischen Auszeichnungen (Muzej Cetinske krajine, Inv. Br B/1373). Zahlreich sind auch Grabsteine mit Darstellung einzelner Waffen und Ausrüstungsgegenstände.

U radu se obrađuju metalni dijelovi vojničke opreme pronađeni u Gardunu, na mjestu rimskog vojnog logora Tilurium. Osobnoj opremi rimskog vojnika pripadaju pojasne kopče, a dijelovi oklopa (spojna kuka i spojna petlja) i kacige (držač perjanice) dio su zaštitne opreme. Najveći broj predmeta su privjesci konjske orme, dok je oružje je zastupljeno samo jednim vrhom strijele. Uz izuzetak strijele koja je datirana u srednjovjekovno razdoblje, sav obrađeni materijal pripada vremenu 1. st.

Background: The network of bone-regulatory cytokines and growth factors affects osteoblast differentiation and activity, thus controlling bone destruction and reparative process. The gene of critical importance in the regulation of bone formation is runt-related transcription factor 2 (Runx2), essential for the expression of the osteoblast-specific gene osteocalcin and osteoblast differentiation. Therefore, the aim of our study was to test if the systemic expression of various bone-regulatory factors including TNF superfamily and BMP family members correlate with the expression of osteoblast differentiation gene Runx2 in different forms of arthritis, depending of the disease activity, applied therapy, arthritis subtype and other clinical parameters. Methods. Three major forms of chronic joint diseases are classified in clinical practice: osteoarthritis (OA), rheumatoid arthritis (RA) and spondyloarthritis (SpA) that includes ankylosing spondylitis (AS), psoriatic arthritis (PA), reactive arthritis, etc. In our study, blood samples were collected from healthy controls (Ctrl ; n = 25, age range 24-61) and RA patients (n = 49, age range 27-57), OA patients (n = 17, age range 45-79) and SpA patients, either with AS (n = 27, age range 32-46) or PA (n = 23, age range 34- 52), after the informed consent. RNA was extracted from PBMCs, amplified by quantitative PCR, and expressed as the relative amounts of RNA for target genes normalized to GPDH. Gene expression values were correlated with the clinical parameters of arthritis. The receiver operating characteristic (ROC) curve analysis was used to determine the efficacy of analyzed genes to discriminate between different types of arthritis and control group. Results. Several of tested immunomodulatory and bone-inducing molecules as well as osteoblast differentiation gene Runx2 were differentially expressed in arthritic patients compared with healthy controls. The greatest difference was found for RA and OA patients that had decreased expression of BMP-4, FasL, LIGHT, TRAIL and Runx2, and OA patients had decreased expression of BMP-6 as well (p

Prikaz kataloga u kojemu su objavljeni arheološki spomenici koji se čuvaju u antičkoj zbirci Muzeja Hrvatskih arheoloških spomenika u Splitu.

Privjesci rimske konjske orme vješali su se pomoću falere ili izravno na remenje konja kako bi pridonijeli dojmu koji je konjanik ostavljao svojom pojavom ; no nisu služili samo kao ukras, nego im se oblikom, detaljima ili prikazima na njima dodavalo simbolično značenje. Najvažnija je bila zaštitna uloga privjesaka, koji su čuvali od zla i nesreće. Obrađeni predmeti pripadaju različitim tipovima privjesaka, a kako su u Muzej dospjeli kao slučajni nalazi pa nam detaljne okolnosti nalaza nisu poznate, datirani su pomoću analognih primjeraka s različitih rimskih lokaliteta. Oprema konja, pa tako i način ukrašavanja ovisili su o statusu konjanika u društvu, odnosno o vojničkom rangu. Od šest ovdje obrađenih privjesaka iz Salone, dva pripadaju lunulastima, dva trodijelnima listolikima, jedan je suzoliki, te jedan srcoliki. Vremenski pripadaju 1. st.

S područja antičke Aserije u splitski Arheološki muzej dospio je određeni broj fibula za koje, nažalost, nemamo precizne okolnosti nalaza. Aucisa fibule, koje su nedavno obavljene u ovom časopisu čine najbrojniju skupinu. U ovoj radnji obrađene su preostale fibule koje, premda malobrojne, pokazuju tipološku raznovrsnost. Zastupljeno je sedam osnovnih tipova predstavljenih različitim varijantama. Uglavnom pripadaju ranijem vremenu (kraj 1. st. pr. Kr., 1. st)., a samo nekoliko ih možemo datirati u kasnije doba, od čega su kasnoantički oblici zastupljeni tek s dvije lukovičaste fibule, no sa stajališta tipologije jednako su zastupljeni oblici 1. i oni 2. st., svaki s po tri različita tipa

Prikaz kataloga fibula u kojem su razni autori objavili zbirku fibula iz Museo civico di Udine. Radi se o fibulama od prapovijesnog do srednjovjekovnog razdoblja.

Prikaz tridesetog, jubilarnog broja časopisa Opuscula archaeologica u kojem nakon prigodnog uvodnog teksta slijede sinteze o proučavanju različitih razdoblja u hrvatskoj arheologiji u posljednjih 50 godina.

Three major forms of chronic joint diseases are classified in clinical practice: osteoarthritis (OA), rheumatoid arthritis (RA) and spondyloarthritis (SpA) that includes several forms (ankylosing spondylitis (AS), psoriatic arthritis (PA), etc.). They differ in the pathophysiological mechanisms and the intensity of cartilage and bone destruction, with RA as a prototype of "destructive" arthritis, OA "steady-state" arthritis and SpA "remodeling" arthritis. The aim of our study was to test changes in the expression of selected bone morphogenetic proteins (BMPs), known for their osteoinductive action, in the peripheral blood mononuclear cells (PBMC) of patients with RA, OA and SpA, and analyze them in relation to the expression of Runx2, an essential transcriptional factor for osteoblast differentiation. Blood samples were collected from healthy controls (Ctrl ; n = 31, age range 24-61) and RA patients (n = 52, age range 27-57), OA patients (n = 15, age range 45-79) and SpA patients, either with AS (n = 26, age range 32-46) or PA (n = 20, age range 34-52), after the informed consent. RNA was extracted from PBMCs, converted to cDNA, amplified by quantitative PCR using TaqMan assays for BMP-2, -4 and Runx2, and expressed as the relative amounts of RNA (mean± SD) for target genes normalized to GPDH. BMP-2 expression was not significantly different among groups, whereas BMP-4 expression was significantly down-regulated in RA and OA patients compared to SpA patients and control subjects (RA 2.35± 1.55 and OA 2.36± 1.80 vs. AS 5.86± 4.67, PA 4.17± 2.44 and Ctrl 5.94± 4.20, p