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Expression of proinflammatory and fibrotic cytokines in synovial tissue during hip osteoarthritis and carpal tunnel syndrome
No full textCiljevi istraživanja: Utvrditi serumsku koncentraciju i lokalni tkivni izražaj upalnih citokina
TNF-α, IL-1ß te fibrotičkih i antifibrotičnih činitelja TGF-ß1 i BMP-7 u sinovijalnoj
membrani zgloba kuka kod osteoartritisa (OA) i subsinovijalnom tkivu kod sindroma
karpalnog tunela (SKT) u bolesnika sa i bez komorbiditeta ove dvije bolesti.
Ispitanici i metode: U istraživanju je sudjelovalo 60 bolesnika zaprimljenih u bolnicu radi
kirurškog liječenja ugradnje totalne endoproteze zgloba kuka zbog OA te kirurške
dekompresije karpalnog tunela kod pacijenata sa SKT. U istraživanju je sudjelovalo 15
zdravih ispitanika kod kojih je mjerena serumska vrijednost istraživanih činitelja te je korišten
kadaverični tkivni materijal na kojem je analiziran tkivni izražaj i lokalizacija istih činitelja.
Imunohistokemijskom metodom utvrđivan je lokalni tkivni izražaj TNF-α, IL-1ß, TGF-ß1 i
BMP-7 u sinovijalnoj membrani kod OA zgloba kuka i subsinovijalnom tkivu kod SKT, a
njihova serumska koncentracija određivana je ELISA metodom.
Rezultati: Serumske razine BMP-7, IL-1β i TNF-α u bolesnika sa SKT, OA i skupini zdravih
ispitanika bila je unutar normalnog raspona i nije se značajno razlikovala među skupinama,
dok je serumska razina TGF-β1 bila značajno viša u skupini SKT bolesnika (16,36 pg/ml;
p<0,0001). Serumska razina BMP-7 bila je značajno viša u bolesnika kojima je
dijagnosticiran OA i SKT u komorbiditetu (2,6 pg/ml, 3,2 pg/ml, p<0,0001). Lokalnog
tkivnog izražaja IL-1ß i TGF-ß1 nije bilo niti u jednoj skupini ispitanika OA i SKT, dok je
umjereni izražaj TNF-α utvrđen u sinoviocitima i perivaskularnoj stromi sinovijalne
membrane OA ispitanika te izraziti izražaj BMP-7 u sinovijalnoj membrani OA ispitanika i u
subsinovijalnom tkivu ispitanika sa SKT.
Zaključak: Rezultati ukazuju na značaj razlika serumskih razina i lokalnog tkivnog izražaja
fibrotičkih i morfogenetskih citokina TGF-ß1 i BMP-7 u bolesnika sa i bez komorbiditeta OA
i SKT.Objectives: To determine the serum concentration and local tissue expression of
inflammatory cytokines TNF-α, IL-1ß and fibrotic and antifibrotic factors TGF-ß1 and BMP -
7 in the synovial membrane of the hip joint in OA and subsynovial tissue in CTS in patients
with and without comorbidity of these two diseases.
Patients and methods: In this study60 patients were participated which were undergoing
surgical treatment for total hip arthroplasty due to severe OA, and surgical decompression of
the carpal tunnel in patients with end stage of CTS. Also, 15 healthy subjects participated in
the research, in whom the serum value of the investigated factors were measured.
Furthermore, cadaveric tissue material was used for the control of tissue expression and
localization of the inflammatory and fibrotic factors. The local tissue expression of TNF-α,
IL-1ß, TGF-ß1 and BMP-7 in the synovial membrane in OA of the hip joint and in the
subsynovial tissue in CTS was determined by the immunohistochemical method, and their
serum concentration was determined by the ELISA method.
Results: The serum levels of BMP-7, IL-1β and TNF-α in patients with CTS, OA and the
group of healthy subjects were within the normal range and did not differ significantly
between these groups, while the serum level of TGF-β1 was significantly higher in the group
of CTS patients (16.36 pg/ml; p < 0.0001). The serum level of BMP-7 was significantly
higher in patients diagnosed with both OA and CTS (2.6 pg/ml, 3.2 pg/ml, p<0.0001). There
was no local tissue expression of IL-1ß and TGF-ß1 in any group of subjects with OA and
CTS, while moderate expression of TNF-α was found in synoviocytes and perivascular
stroma of the synovial membrane of OA subjects, and strong expression of BMP-7 both in the
synovial membrane of OA subjects and in the subsynovial tissue of subjects with CTS.
Conclusion: The results indicate the significance of differences in serum levels and local
tissue expression of fibrotic and morphogenic cytokines TGF-ß1 and BMP-7 in patients with
and without comorbidities of OA and SKT
Expression of osteoinductive proteins and their inhibitors during osteogenesis
No full textCilj istraživanja. Cilj ovoga istraživanja bio je utvrditi vremensku i histološku distribuciju izražaja koštanih morfogenetskih proteina 2, 4 i 7 i njihovih inhibitora (gremlin, nogin, hordin i folistatin) tijekom procesa normalne, (ektopično) inducirane i patološke osteogeneze. Materijal i metode. Istraživanje je provedeno na humanom i animalnom materijalu. Dvadeset uzoraka osteofita i pripadajućeg dijela sinovijalne membrane koljenoga zgloba uzeto je od dvadeset pacijenata koji su podvrgnuti kiruškom zahvatu ugradnje umjetnog zgloba (totalna endoproteza koljena) na Klinici za ortopediju Lovran. Dvadeset uzoraka normalne zglobne hrskavice s pripadajućim subhondralnim koštanim tkivom i sinovijalnom membranom zglobne čahure uzeto je iz koljenog zgloba smrtno stradalih osoba obduciranih na Zavodu za sudsku medicinu i kriminalistiku Medicinskog fakulteta u Rijeci. Uzorci su uzeti iz koljenih zglobova bez makroskopskih znakova degenerativnih i upalnih promjena. Za istraživanja na animalnom materijalu korišteno je 150 ženki Hannover – Wistar štakora, starosti tri mjeseca i mase 300 g. Životinjama je potkožno u grudnoj regiji (na ektopičnom mjestu) bilateralno ugrađen usadak demineraliziranog koštanog matriksa. U istraživanju su korištene metode imunohistokemije i Western blot. Rezultati. Koštani morfogenetski proteini 2, 4 i 7 različito su izraženi tijekom faza inducirane ektopične osteogeneze. U ranoj fazi osteogeneze izrazito su izraženi BMP-2 i BMP-4, a tijekom kasnije faze pojačava se izražaj BMP-7. Inhibitori koštanih morfogenetskih proteina (nogin, hordin, gremlin i folistatin) su koeksprimirani s ispitivanim BMP tijekom svih faza osteogeneze. U vezivnoj membrani usadka razina izražaja pojedinih inhibitora je konstantna tijekom cijelog procesa ektopične osteogeneze, iako su razine izražaja među inhibitorima različite. U hondrocitima osteofita BMP-7 je jače izražen u odnosu na BMP-4, dok BMP-2 nije izražen. Inhibitori BMP su u hondrocitima osteofita koeksprimirani s BMP. U stanicama koštanog tkiva osteofita je izražaj BMP i njihovih inhibitora minimalan.
Zaključak. Tijekom osteogeneze (fiziološka, patološka, ektopična) obrasci izražaja koštanih morfogenetskih proteina i njihovih inhibitora u hrskavičnom i koštanom tkivu su specifični i bitno različiti. Složeno lokalno međudjelovanje ovih proteina uvijek je usmjereno u pravcu održavanja, odnosno uspostavljanja lokalne homeostaze koštanog tkiva. Pored lokalnih međudjelovanja, BMP i njihovi inhibitori, te stanice na čiju aktivnost oni utječu, ovisni su i o sistemskim činiteljima (npr. hormonima). Drugim riječima, iako je neposredno djelovanje ispitivanih proteina, BMP s jedne strane i njihovih inhibitora s druge strane, antagonističko, u cjelini gledano, njihova je uloga sinergistička i usmjerena u pravcu homestaze koštanog tkiva odnosno koštanog sustava, a time i organizma u cjelini.Aim. The aim of this investigation was to determine temporal and histological distribution of the expression of bone morphogenetic proteins 2, 4 and 7, and their inhibitors (gremlin, noggin, chordin and follistatin) during normal, induced (ectopically), and pathological osteogenesis. Material and methods. The investigation was conducted on human and animal material. Twenty samples of osteophytes and associated parts of the synovial membrane of the knee joint were obtained from 20 patients who underwent artificial joint implant surgery (total knee endoprosthesis) at the Orthopedic clinic in Lovran. Twenty samples of normal articular cartilage with associated subchondral bone and the synovial membrane of the joint capsule were taken from the knee joint of deceased persons following autopsy at the Institute of forensic medicine and crime investigation at the Faculty of Medicine in Rijeka. The samples were harvested from knee joints without macroscopic signs of degenerative and inflammatory changes. The investigation on the animal material included 150 female Hannover – Wistar rats, 3 months of age and 300 g of weight. The animals were implanted demineralized bone matrix subcutaneously at bilateral ectopic place in the chest region. Protein expression and localization was determined by immunohistochemical analysis and Western blot.
Results. The expression of bone morphogenetic proteins 2, 4 and 7 varied during developmental phases of ectopic osteogenesis. In the early phase of osteogenesis, BMP-2 and BMP-4 were significantly expressed, whereas during the late phase, the expression of BMP-7 increased. Inhibitors of bone morphogenetic protein (noggin, chordin, gremlin i follistatin) were co-expressed with the studied BMP during all phases of osteogenesis. The level of expression of specific inhibitors in the connective membrane of the implant was constant during the whole process of ectopic osteogenesis, although the expression levels between inhibitors varied. In chondrocytes in the osteophytes, BMP-7 was more expressed than BMP-4, while BMP-2 was not expressed. BMP inhibitors in chondrocytes of the osteophytes were co-expressed with BMP. The expression of BMP and their inhibitors in the cells of bone tissue osteophytes was minimal.
Conclusion. During different processes of osteogenesis (physiological, pathological, ectopic) the expression patterns of bone morphogenetic proteins and their inhibitors in cartilage and bone tissue were specific and markedly different. Complex local interaction of these proteins is always directed to the establishment and maintenance of local homeostasis of bone tissue. Besides local interaction, BMP and their inhibitors, and the cells whose activity they affect depend on systemic factors (e.g. hormones). In other words, although the studied proteins – BMP and their inhibitors exhibit immediate antagonistic activity, as a whole, their role is synergistic and involved in the homeostasis of bone tissue, i.e. the skeletal system and, thus, the organism as a whole
Expression of proinflammatory and fibrotic cytokines in synovial tissue during hip osteoarthritis and carpal tunnel syndrome
No full textCiljevi istraživanja: Utvrditi serumsku koncentraciju i lokalni tkivni izražaj upalnih citokina
TNF-α, IL-1ß te fibrotičkih i antifibrotičnih činitelja TGF-ß1 i BMP-7 u sinovijalnoj
membrani zgloba kuka kod osteoartritisa (OA) i subsinovijalnom tkivu kod sindroma
karpalnog tunela (SKT) u bolesnika sa i bez komorbiditeta ove dvije bolesti.
Ispitanici i metode: U istraživanju je sudjelovalo 60 bolesnika zaprimljenih u bolnicu radi
kirurškog liječenja ugradnje totalne endoproteze zgloba kuka zbog OA te kirurške
dekompresije karpalnog tunela kod pacijenata sa SKT. U istraživanju je sudjelovalo 15
zdravih ispitanika kod kojih je mjerena serumska vrijednost istraživanih činitelja te je korišten
kadaverični tkivni materijal na kojem je analiziran tkivni izražaj i lokalizacija istih činitelja.
Imunohistokemijskom metodom utvrđivan je lokalni tkivni izražaj TNF-α, IL-1ß, TGF-ß1 i
BMP-7 u sinovijalnoj membrani kod OA zgloba kuka i subsinovijalnom tkivu kod SKT, a
njihova serumska koncentracija određivana je ELISA metodom.
Rezultati: Serumske razine BMP-7, IL-1β i TNF-α u bolesnika sa SKT, OA i skupini zdravih
ispitanika bila je unutar normalnog raspona i nije se značajno razlikovala među skupinama,
dok je serumska razina TGF-β1 bila značajno viša u skupini SKT bolesnika (16,36 pg/ml;
p<0,0001). Serumska razina BMP-7 bila je značajno viša u bolesnika kojima je
dijagnosticiran OA i SKT u komorbiditetu (2,6 pg/ml, 3,2 pg/ml, p<0,0001). Lokalnog
tkivnog izražaja IL-1ß i TGF-ß1 nije bilo niti u jednoj skupini ispitanika OA i SKT, dok je
umjereni izražaj TNF-α utvrđen u sinoviocitima i perivaskularnoj stromi sinovijalne
membrane OA ispitanika te izraziti izražaj BMP-7 u sinovijalnoj membrani OA ispitanika i u
subsinovijalnom tkivu ispitanika sa SKT.
Zaključak: Rezultati ukazuju na značaj razlika serumskih razina i lokalnog tkivnog izražaja
fibrotičkih i morfogenetskih citokina TGF-ß1 i BMP-7 u bolesnika sa i bez komorbiditeta OA
i SKT.Objectives: To determine the serum concentration and local tissue expression of
inflammatory cytokines TNF-α, IL-1ß and fibrotic and antifibrotic factors TGF-ß1 and BMP -
7 in the synovial membrane of the hip joint in OA and subsynovial tissue in CTS in patients
with and without comorbidity of these two diseases.
Patients and methods: In this study60 patients were participated which were undergoing
surgical treatment for total hip arthroplasty due to severe OA, and surgical decompression of
the carpal tunnel in patients with end stage of CTS. Also, 15 healthy subjects participated in
the research, in whom the serum value of the investigated factors were measured.
Furthermore, cadaveric tissue material was used for the control of tissue expression and
localization of the inflammatory and fibrotic factors. The local tissue expression of TNF-α,
IL-1ß, TGF-ß1 and BMP-7 in the synovial membrane in OA of the hip joint and in the
subsynovial tissue in CTS was determined by the immunohistochemical method, and their
serum concentration was determined by the ELISA method.
Results: The serum levels of BMP-7, IL-1β and TNF-α in patients with CTS, OA and the
group of healthy subjects were within the normal range and did not differ significantly
between these groups, while the serum level of TGF-β1 was significantly higher in the group
of CTS patients (16.36 pg/ml; p < 0.0001). The serum level of BMP-7 was significantly
higher in patients diagnosed with both OA and CTS (2.6 pg/ml, 3.2 pg/ml, p<0.0001). There
was no local tissue expression of IL-1ß and TGF-ß1 in any group of subjects with OA and
CTS, while moderate expression of TNF-α was found in synoviocytes and perivascular
stroma of the synovial membrane of OA subjects, and strong expression of BMP-7 both in the
synovial membrane of OA subjects and in the subsynovial tissue of subjects with CTS.
Conclusion: The results indicate the significance of differences in serum levels and local
tissue expression of fibrotic and morphogenic cytokines TGF-ß1 and BMP-7 in patients with
and without comorbidities of OA and SKT
Tehnike poticanja osteogeneze u svrhu osteointegracije dentalnih implantata
No full textGubitak zuba zbog kariesa, trauma ili uznapredovale parodontne bolesti, dovodi do resorpcije alveolarnog grebena, odnosno smanjenja volumena i promjene u morfologiji koštanog tkiva. Ponovna uspostava žvačnog sustava može se postići postavljanjem dentalnih implantata na mjesta izgubljenih zubi. Glavni problem koji se javlja pri tome je nedostatak kosti u horizontalnom i/ili vertikalnom smjeru koji ne dozvoljava postavu implantata na anatomsko mjesto gdje se nalazio zub. Ponovna uspostava anatomskih odnosa se može postići stimulacijom rasta kosti. Rast kosti se može stimulirati kirurškim tehnikama poput splitkrest osteotomije, vođene regeneracije kosti, sinus lifta i bone grafta, i uporabom augmentacijskih materijala i faktora rasta. Za postavljanje idealnog plana terapije potrebno je razumijevanje procesa koštanog modeliranja, remodeliranja i cijeljenja, i poznavanje svih materijala koji se koriste u tu svrhu.The loss of a tooth due to caries, trauma or advanced periodontal desease causes alveolar ridge resorption, decrease in its volume and change in morphology. Restauration of the masticatory aparatus can be accomplished by placement of dental implants in places of lost teeth. The main problem that appears is bone mass deficiency in horizontal and/or vertical direction. Restaurtion of anatomical proprotions can be maintained by stimulating bone formation. Bone formation can be stimulated with surgical procedures such as splitcrest osteotomy, guided bone regeneration, sinus lift or bone grafting, and the use of bone augmentation materials and growt factors. There is no ideal way of success all techniques and materials have their benefits and their disadvantages. The perfect resoult can be achieved by individual approach for each case and by combination of different materials and their benefits. In order to obtain an ideal plan, knowledge and understanding about processes of bone modeling, remodeling and healing, and about all materials used for its purpouse are necessary
Expression of proinflammatory and fibrotic cytokines in synovial tissue during hip osteoarthritis and carpal tunnel syndrome
No full textCiljevi istraživanja: Utvrditi serumsku koncentraciju i lokalni tkivni izražaj upalnih citokina
TNF-α, IL-1ß te fibrotičkih i antifibrotičnih činitelja TGF-ß1 i BMP-7 u sinovijalnoj
membrani zgloba kuka kod osteoartritisa (OA) i subsinovijalnom tkivu kod sindroma
karpalnog tunela (SKT) u bolesnika sa i bez komorbiditeta ove dvije bolesti.
Ispitanici i metode: U istraživanju je sudjelovalo 60 bolesnika zaprimljenih u bolnicu radi
kirurškog liječenja ugradnje totalne endoproteze zgloba kuka zbog OA te kirurške
dekompresije karpalnog tunela kod pacijenata sa SKT. U istraživanju je sudjelovalo 15
zdravih ispitanika kod kojih je mjerena serumska vrijednost istraživanih činitelja te je korišten
kadaverični tkivni materijal na kojem je analiziran tkivni izražaj i lokalizacija istih činitelja.
Imunohistokemijskom metodom utvrđivan je lokalni tkivni izražaj TNF-α, IL-1ß, TGF-ß1 i
BMP-7 u sinovijalnoj membrani kod OA zgloba kuka i subsinovijalnom tkivu kod SKT, a
njihova serumska koncentracija određivana je ELISA metodom.
Rezultati: Serumske razine BMP-7, IL-1β i TNF-α u bolesnika sa SKT, OA i skupini zdravih
ispitanika bila je unutar normalnog raspona i nije se značajno razlikovala među skupinama,
dok je serumska razina TGF-β1 bila značajno viša u skupini SKT bolesnika (16,36 pg/ml;
p<0,0001). Serumska razina BMP-7 bila je značajno viša u bolesnika kojima je
dijagnosticiran OA i SKT u komorbiditetu (2,6 pg/ml, 3,2 pg/ml, p<0,0001). Lokalnog
tkivnog izražaja IL-1ß i TGF-ß1 nije bilo niti u jednoj skupini ispitanika OA i SKT, dok je
umjereni izražaj TNF-α utvrđen u sinoviocitima i perivaskularnoj stromi sinovijalne
membrane OA ispitanika te izraziti izražaj BMP-7 u sinovijalnoj membrani OA ispitanika i u
subsinovijalnom tkivu ispitanika sa SKT.
Zaključak: Rezultati ukazuju na značaj razlika serumskih razina i lokalnog tkivnog izražaja
fibrotičkih i morfogenetskih citokina TGF-ß1 i BMP-7 u bolesnika sa i bez komorbiditeta OA
i SKT.Objectives: To determine the serum concentration and local tissue expression of
inflammatory cytokines TNF-α, IL-1ß and fibrotic and antifibrotic factors TGF-ß1 and BMP -
7 in the synovial membrane of the hip joint in OA and subsynovial tissue in CTS in patients
with and without comorbidity of these two diseases.
Patients and methods: In this study60 patients were participated which were undergoing
surgical treatment for total hip arthroplasty due to severe OA, and surgical decompression of
the carpal tunnel in patients with end stage of CTS. Also, 15 healthy subjects participated in
the research, in whom the serum value of the investigated factors were measured.
Furthermore, cadaveric tissue material was used for the control of tissue expression and
localization of the inflammatory and fibrotic factors. The local tissue expression of TNF-α,
IL-1ß, TGF-ß1 and BMP-7 in the synovial membrane in OA of the hip joint and in the
subsynovial tissue in CTS was determined by the immunohistochemical method, and their
serum concentration was determined by the ELISA method.
Results: The serum levels of BMP-7, IL-1β and TNF-α in patients with CTS, OA and the
group of healthy subjects were within the normal range and did not differ significantly
between these groups, while the serum level of TGF-β1 was significantly higher in the group
of CTS patients (16.36 pg/ml; p < 0.0001). The serum level of BMP-7 was significantly
higher in patients diagnosed with both OA and CTS (2.6 pg/ml, 3.2 pg/ml, p<0.0001). There
was no local tissue expression of IL-1ß and TGF-ß1 in any group of subjects with OA and
CTS, while moderate expression of TNF-α was found in synoviocytes and perivascular
stroma of the synovial membrane of OA subjects, and strong expression of BMP-7 both in the
synovial membrane of OA subjects and in the subsynovial tissue of subjects with CTS.
Conclusion: The results indicate the significance of differences in serum levels and local
tissue expression of fibrotic and morphogenic cytokines TGF-ß1 and BMP-7 in patients with
and without comorbidities of OA and SKT
GENDER-RELATED DIFFERENCES IN EXPRESSION OF BONE MORPHOGENETIC PROTEINS AND THEIR INHIBITORS WITHIN JOINT-HIPPOCAMPAL AXIS IN PRISTANE-INDUCED ARTHRITIS
No full textCiljevi istraživanja: Utvrditi spolne razlike u izražajima BMP-ova (BMP-4, -7) i njihovih inhibitora (Noggin, Gremlin) u sinovijalnoj membrani, zglobnoj hrskavici i u dentatnoj vijugi hipokampusa, te u intenzitetu adultne neurogeneze i razinama upalnih citokina (TNF-α i IL-17A) u krvi kao i njihovu međusobnu korelaciju tijekom tri faze artritisa induciranog pristanom (PIA) – na početku, na vrhuncu i u remisiji. Materijali i metode: Istraživanje je provedeno na 140 Dark Agouti štakora, starosti 7 – 8 tjedana. Analizirani su uzorci mozga, stražnjih stopala i serum. Izražaj BMP-ova i inhibitora te intenzitet adultne neurogeneze određen je imunohistokemijski s kvantifikacijskom analizom, a razina citokina ELISA-om. Stupanj upale u zglobu određen je Krenn-ovom i Mankin-ovom semikvantitaivnom skalom. Rezultati su statistički obrađeni jednosmjernom analizom varijance (ANOVA), Mann-Whitney U test-om i Pearson-ovom korelacijom (r). Podatci su izraženi kao srednja vrijednost ± SD, a statisička značajnost uzeta pri vrijednosti p < 0,05. Rezultati: PIA je započela ranije u mužjaka, ali je tijekom remisije u ženki utvrđena manja regresija znakova upale. PIA je uzrokovala veći porast izražaja BMP-4, Noggin-a i Gremlin-a u zglobnoj hrskavici ženki te veći pad BMP-7 u mužjaka. Sinovijalna upala te izražaj BMP-ova i inhibitora su bili veći u ženki. U hipokampusu PIA je uzrokovala porast izražaja BMP-4, i pad BMP-7 i Noggin-a u mužjaka, a u ženki pad BMP-4 i Noggin-a. Porast IL-17A u krvi na početku PIA bio je veći u mužjaka, a u ženki porast TNF-α je bio veći u remisiji. U ženki je tijekom remisije došlo do značajno većeg porasta broja Ki-67+ , DCX+ i SOX-2 + stanica i omjera DCX/Ki-67 u subgranularnoj zoni dentatne vijuge u odnosu na mužjake. Zaključci: Rezultati dokazuju postojanje spolnih razlika u izražaju BMP-ova i njihovih inhibitora unutar zglobno-hipokampalne osi, te u razinama TNF-α i IL-17A u krvi. Nadalje, rezultati dokazuju razliku u korelaciji BMP-ova i inhibitora u zglobu i dentatnoj vijugi s intenzitetom adultne neurogeneze, upalom u zglobu i razinama citokina među spolovima. To ukazuje na postojanje različitih mehanizama nastanka i razvoja bolesti, a time i potencijalnih pridruženih neuropsihijatrijskih komplikacija između spolova u sklopu modela reumatoidnog artritisa. Ključne riječi: adultna neurogeneza; koštani morfogenetski proteini; artritis induciran pristanom;Objectives: To determine gender differences in the expression of BMPs (BMP-4, -7) and their inhibitors (Noggin, Gremlin) in the synovial membrane, articular cartilage and dentate gyrus of the hippocampus, and in the intensity of adult neurogenesis and levels of inflammatory cytokines (TNF-α and IL-17A) in the blood as well as their correlation with each other during three stages of pristane-induced arthritis (PIA) - at the onset, at the peak and in remission. Materials and methods: The study was conducted on 140 Dark Agouti rats, aged 7-8 weeks. Brain, hindfoot, and serum samples were analyzed. The expression of BMPs and inhibitors and the intensity of adult neurogenesis were determined immunohistochemically by quantification analysis, and cytokine levels by ELISA. The degree of inflammation in the joint was determined by Krenn and Mankin semiquantitative scoring. The results were statistically processed by one-way analysis of variance (ANOVA), Mann-Whitney U test and Pearson's correlation (r). Data were expressed as mean ± SD, and statistical significance was taken at p <0.05.
Results: The onset of PIA was earlier in males, and they recovered better during remission. BMP-4, Noggin, and Gremlin in the articular cartilage during PIA were upregulated more in females, and BMP-7 was downregulated more in males. Synovial inflammation and synovial BMPs and their inhibitors were upregulated more in females. PIA caused hippocampal BMP-4 upregulation and downregulation of BMP 7 and Noggin in males, and in females BMP-4 and Noggin were downregulated. The increase in IL-17A at the onset of PIA was higher in males, and in females the increase in TNF-α was higher in remission. During remission, females had a significantly higher increase in the number of Ki-67+ , DCX+ and SOX-2 + cells and the DCX/Ki-67 ratio in the subgranular zone of dentate gyrus compared to males. Conclusions: Results show gender differences in the expression of BMPs and their inhibitors within the joint-hippocampus axis, and in the levels of TNF-α and IL-17A in the blood. Furthermore, the results demonstrate differences in correlations of BMPs and inhibitors in the joint and dentate gyrus with the intensity of adult nerogenesis and inflammation between genders. This indicates the existence of different mechanisms of disease onset and development, and thus potential associated neuropsychiatric complications of rheumatoid arthritis between genders
Uloga koštanog morfogenetskog proteina -7 u ektopičnoj i ortotopičnoj osteogenezi u štakora : doktorska disertacija
No full textSažetak disertacije "Uloga koštanog morfogenetskog proteina -7 u ektopičnoj i ortotopičnoj osteogenezi u štakora" nije dostupan
Uloga koštanog morfogenetskog proteina -7 u ektopičnoj i ortotopičnoj osteogenezi u štakora : doktorska disertacija
No full textSažetak disertacije "Uloga koštanog morfogenetskog proteina -7 u ektopičnoj i ortotopičnoj osteogenezi u štakora" nije dostupan
Bone biopsy and histomorphometry as a tool for diagnosis of osteoporosis and other metabolic bone diseases
Full text linkOsteoporoza je sistemska bolest skeleta karakterizirana redukcijom koštane mase i poremećajem unutrašnje arhitekture koštanog tkiva, što dovodi do povećane fragilnosti kostiju i sklonosti prijelomima. Prema WHO, glavni dijagnostički kriterij za osteoporozu je BMD za lumbalni dio kralježnice i femur više od 2,5 SD ispod normalne vrijednosti koštane mase referentne za određenu starosnu dob. Statistički izvještaji govore da je danas u Hrvatskoj oko 250.000 žena oboljelo od osteoporoze. Prema službenim smjernicama za dijagnostiku, prevenciju i liječenje osteoporoze u RH, u dijagnostici osteoporoze, pored denzitometrije, rendgenograma torako-lumbalne kralježnice te laboratorijskih pokazatelja pregradnje kosti, preporučuje se i biopsija kosti s histomorfometrijom. Cilj je ovog rada uputiti na metodu koštane biopsije i histomorfometrije i njenu vrijednost u dijagnostici, ali i praćenju liječenja metaboličkih bolesti kostiju i osteoporoze.Osteoporosis is systemic skeletal disease characterised by reduction of bone mass as well as disruption of internal architecture of the osseous tissue which leads to increased bone fragility and tendency for fracture. According to WHO the primary diagnostic criteria for osteoporosis is BMD more than 2,5 SD below normal values of bone mass referral for certain age, measured on lumbar spine and femoral bone. Over 250.000 women are diagnosed with osteoporosis in Croatia. According to guidance for osteoporosis diagnosis, prevention and treatment, except for bone densitometry, X-rays of thoraco-lumbar spine and biochemical markers of bone remodeling, bone biopsy and histomorphometry are suggested. The aim of this paper is to describe bone biopsy and histomorphometry as a valuable method for diagnostics and follow up in metabolic bone diseases and osteoporosis
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