Cilj 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.