BMPs regulate synovial quiescence and adult neurogenesis in the hippocampus in non-stress conditions. However, changes in BMP expression that are induced by inflammation during rheumatoid arthritis ...(RA) have not yet been reported. Here, we show that signalling with synovial BMPs (BMP-4 and -7) mediates the effect of systemic inflammation on adult neurogenesis in the hippocampus during pristane-induced arthritis (PIA) in
(DA) rats, an animal model of RA. Moreover, we show gender differences in BMP expressions and their antagonists (Noggin and Gremlin) during PIA and their correlations with the clinical course and IL-17A and TNF-α levels in serum. Our results indicate gender differences in the clinical course, where male rats showed earlier onset and earlier recovery but a worse clinical course in the first two phases of the disease (onset and peak), which correlates with the initial increase of serum IL-17A level. The clinical course of the female rats worsened in remission. Their prolonged symptoms could be a reflection of an increased TNF-α level in serum during remission. Synovial inflammation was greater in females in PIA-remission with greater synovial BMP and antagonist expressions. More significant correlations between serum cytokines (IL-17A and TNF-α), and synovial BMPs and their antagonists were found in females than in males. On the other hand, males showed an increase in hippocampal BMP-4 expression during the acute phase, but both genders showed a decrease in antagonist expressions during PIA in general. Both genders showed a decrease in the number of Ki-67
and SOX-2
and DCX
cells and in the ratio of DCX
to Ki67
cells in the dentate gyrus during PIA. However, in PIA remission, females showed a faster increase in the number of Ki67
, SOX-2
, and DCX
cells and a faster increase in the DCX/Ki67 ratio than males. Both genders showed an increase of hippocampal BMP-7 expression during remission, although males constantly showed greater BMP-7 expression at all time points. Our data show that gender differences exist in the BMP expressions in the periphery-hippocampus axis and in the IL-17A and TNF-α levels in serum, which could imply differences in the mechanisms for the onset and progression of the disease, the clinical course severity, and adult neurogenesis with subsequent neurological complications between genders.
It is not entirely clear how the interaction between joint inflammation and the central nervous system (CNS) response in rheumatoid arthritis (RA) works, and what pathophysiology underlies the sex ...differences in coexisting neuropsychiatric comorbidities. It is known that estrogen hormones reduce inflammation in RA and that this occurs mainly via the stimulation of G protein-coupled receptor-30 (GPR30), also known as G protein-coupled estrogen receptor (GPER) 1. However, changes in GPR30 expression and sex differences induced by local and systemic inflammation in RA are not yet known. Our aim was to reveal sex differences in the expression and association of joint GPR30 with local and systemic inflammation, clinical course and furthermore with hippocampal GPR30 expression during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Furthermore, we demonstrated sex-specific differences in the association between joint and systemic inflammation and hippocampal microglia during PIA. Our results suggest sex-specific differences not only in the clinical course and serum levels of pro-inflammatory cytokines but also in the expression of GPR30. Female rats show greater synovial inflammation and greater damage to the articular cartilage compared to males during PIA attack. Male rats express higher levels of synovial and cartilaginous GPR30 than females during PIA, which correlates with a less severe clinical course. The correlation between synovial and cartilaginous GPR30 and joint inflammation scores (Krenn and Mankin) in male rats suggests that the more severe the joint inflammation, the higher the GPR30 expression. At the same time, there is no particular upregulation of hippocampal GPR30 in males. On the other hand, female rats express higher levels of neuroprotective GPR30 in the hippocampus than male rats at the basic level and during PIA attack. In addition, females have a higher number of Iba-1+ cells in the hippocampus during PIA attack that strongly correlates with the clinical score, serum levels of IL-17A, and Krenn and Mankin scores. These results suggest that male rats are better protected from inflammation in the joints and female rats are better protected from the inflammation in the hippocampus during a PIA attack, independently of microglia proliferation. However, in the remission phase, synovial GPR30 expression suddenly increases in female rats, as does hippocampal GPR30 expression in males. Further experiments with a longer remission period are needed to investigate the molecular background of these sex differences, as well as microglia phenotype profiling.
This prospective, randomized, controlled clinical trial reports clinical, radiographic, histologic and immunohistochemical results of autologous dentin graft (ADG) and its comparison with a mixture ...of bovine xenograft with autologous bone (BX+AB). After tooth extraction in the esthetic zone of maxilla, the alveolar ridge of 20 patients in the test group was augmented with ADG, while 17 patients in the control group received the combination of BX+AB. Cone beam computed tomography (CBCT) was performed before tooth extraction and after 4 months when a total of 22 bone biopsies were harvested and subjected to histological and immunohistochemical analysis. Radiological analysis showed comparable results of bone dimension loss in both groups. Quantitative histologic analysis showed comparable results with no statistically significant differences between the groups. Immunohistochemical staining with TNF-α and BMP-4 antibodies revealed immunopositivity in both groups. A statistically significant difference between the groups was found in the intensity of TNF-α in the area of newly formed bone (
= 0.0003) and around remaining biomaterial particles (
= 0.0027), and in the intensity of BMP-4 in the area around biomaterial particles (
= 0.0001). Overall, ADG showed biocompatibility and achieved successful bone regeneration in the esthetic zone of the maxilla similar to BX+AB.
Xenogeneic biomaterials Cerbone® and OsteoBiol® are widely used in oral implantology. In dental practice, xenogeneic biomaterial is usually combined with autologous bone to provide bone volume ...stability needed for long-term dental implants. Magnesium alloy implants dissolve and form mineral corrosion layer that is directly in contact with bone tissue, allowing deposition of the newly formed bone. CSBD heals by intramembranous ossification and therefore is a convenient model for analyses of ostoconductive and osteoinductive properties of different type of biomaterials. Magnesium alloy-enriched biomaterials have not yet been applied in oral implantology. Therefore, the aim of the current study was to investigate biological properties of potentially new bovine xenogeneic biomaterial enriched with magnesium alloy in a 5 mm CSBD model. Osteoconductive properties of Cerabone®, Cerabone® + Al. bone, and OsteoBiol® were also analyzed. Dynamics of bone healing was followed up on the days 3, 7, 15, 21, and 30. Calvary bone samples were analyzed by micro-CT, and values of the bone morphometric parameters were assessed. Bone samples were further processed for histological and immunohistochemical analyses. Histological observation revealed CSBD closure at day 30 of the given xenogeneic biomaterial groups, with the exception of the control group. TNF-α showed high intensity of expression at the sites of MSC clusters that underwent ossification. Osx was expressed in pre-osteoblasts, which were differentiated into mature osteoblasts and osteocytes. Results of the micro-CT analyses showed linear increase in bone volume of all xenogeneic biomaterial groups and also in the control. The highest average values of bone volume were found for the Cerabone® + Mg group. In addition, less residual biomaterial was estimated in the Cerabone® + Mg group than in the Cerabone® group, indicating its better biodegradation during CSBD healing. Overall, the magnesium alloy xenogeneic biomaterial demonstrated key properties of osteoinduction and biodegradidibility during CSBD healing, which is the reason why it should be recommended for application in clinical practice of oral implantology.
Autologous dentin is frequently used in guided bone regeneration due to its osteoinductive properties, which come from its similarity to native bone. On the other hand, the xenogeneic bone ...biomaterial Cerabone
serves as a biocompatible, but hardly resorbed biomaterial. During bone healing, an inflammatory, vascular, and osteogenic response occurs in which cytokines such as tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and osteopontin (OPN) are released locally and systemically. The aim was to follow up the dynamics (on days 3, 7, 15, 21, and 30) of critical-sized bone defect (CSBD) healing after the implantation of bovine devitalized dentin, rat dentin, and xenogeneic bone biomaterial. For this purpose, histological and histomorphometric methods were employed. Additionally, serum concentrations of TNF-α, VEGF, and OPN were monitored in parallel to better understand the biomaterial-dependent systemic response in rats. At the last time interval, the results showed that the bone defect was bridged over in all three groups of biomaterials. The rat dentin group had the highest percentage of bone volume (BV/TV) and the least percentage of residual biomaterial (RB), which makes it the most optimal biomaterial for bone regeneration. Serum concentrations of the TNF-α, VEGF, and OPN refer to systemic response, which could be linked to intense bone remodeling between days 15 and 21 of the bone healing.
A certain percentage of carpal tunnel syndrome (CTS) is associated with inflammatory conditions. Osteoarthritis (OA) increases the risk of CTS, and both diseases are common in the general population. ...Moreover, OA and CTS are often present in the same patients. Since inflammation and fibrosis are found in both conditions, the question is whether circulating inflammatory cytokines and cytokines involved in fibrosis in OA and CTS patients could serve as indicators of coexisting CTS and OA pathology. This investigation was performed on 31 CTS patients, 29 hip OA patients, and 15 healthy volunteers. Blood samples were collected, and serum levels of TGF-β1, BMP-7, IL-1β, and TNFα were measured using the ELISA method. The statistical analysis was performed to reveal the most significant differences in the serum levels of these cytokines. Statistical significance was set at p-values ≤ 0.05. The serum level of TGF-β1 was the highest in CTS patients (16.36 pg/mL) and significantly different compared to OA and healthy control. Analysis of the cytokine serum level in the subdivided group revealed that serum levels of TGF-β1 and BMP-7 were significantly higher in CTS+/OA+ patients as well as BMP-7 in the OA+/CTS+ group. There was no significant difference in serum levels of the inflammatory cytokines TNFα and IL-1β among all groups. This study showed that in the end stage of CTS and OA, serum levels of inflammatory cytokines (IL1-β and TNFα) were not altered, while the serum levels of TGF-β1 and BMP-7 were significantly higher, especially in patients with coexisting OA and CTS. These findings suggest the possible values of TGF-β1 and BMP-7 as a predictive factor for the comorbidity of CTS and OA.
Beyond stimulating bone formation, bone morphogenetic proteins (BMPs) are important in development, inflammation, and malignancy of the gut. We have previously shown that BMP7 has a regenerative, ...anti-inflammatory, and antiproliferative effect on experimental inflammatory bowel disease (IBD) in rats. To further investigate the BMP signaling pathway we monitored the effect of BMP7 therapy on the BMP signaling components in the rat colon during different stages of experimentally induced colitis by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The results showed a significantly decreased BMP7 expression in the acute phase, followed by a significantly increased BMP2 and decreased BMP6 expression during the chronic phase of colitis. BMP7 therapy influenced the expression of several BMPs with the most prominent effect on downregulation of BMP2 and upregulation of BMP4 in the chronic phase of colitis. Importantly, connective tissue growth factor and noggin expression were elevated in the acute stage and significantly decreased upon BMP7 therapy. BMP receptor I expression was unchanged, whereas BMP receptor II was decreased at day 2 and increased at days 14 and 30 of TNBS inflammation. However, an opposite pattern of expression following BMP7 therapy has been observed. BMP7 increased the expression of BR-Smad including Smad3 and Smad4. Inhibitory Smads were increased in colitis and significantly decreased following BMP7 therapy at later stages of the disease. We suggest that BMP signaling was altered during TNBS-induced colitis and was recovered with BMP7 administration, suggesting that IBD is a reversible process.
Pregradnja koštanog sustava Zoričić Cvek, Sanja; Bobinac, Dragica; Đudarić, Luka ...
Medicina fluminensis,
12/2015, Letnik:
51, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Koštani sustav kralježnjaka vrši dvije glavne uloge: prva je biomehanička uloga koja uključuje podupiranje tijela i zaštitu unutarnjih organa i struktura te inzerciju mišićima u svrhu izvođenja ...pokreta, a druga uloga je metabolička koja uključuje održavanje mineralne homeostaze organizma. Zato, iako su smatrane „mrtvim” inertnim strukturama, kao što to studenti tijekom svog studija medicine doživljavaju, kosti su metabolički iznimno aktivni organi podvrgnuti kontinuiranim cjeloživotnim promjenama. Tijekom rasta i razvoja kosti se formiraju procesom oblikovanja (engl. bone modeling), što uključuje izgradnju i odlaganje koštanog matriksa na razvojno određenim i biomehanički induciranim mjestima skeleta. Čak i prije negoli se skelet u potpunosti razvije, kosti se počinju kontinuirano pregrađivati (engl. bone remodeling) u svrhu održavanja tkivnog integriteta i biomehaničke funkcije, prilagodbe koštane arhitekture prema mehaničkim zahtjevima i zbog popravaka mikrooštećenja, te ako je potrebno mobilizirati kalcij i fosfor. Proces pregradnje uključuje niz precizno reguliranih i tijesno spregnutih staničnih i molekularnih procesa koje omogućuje koordinirana aktivnost osteocita, osteoblasta i osteoklasta. Ova tri različita tipa stanica koštanog tkiva organizirana su u specifičnu morfološku i funkcionalnu višestaničnu jedinicu (engl. basic multicellular unit) koja obavlja i koordinira dva temeljna procesa u biologiji kosti: razgradnju i izgradnju kosti tijekom ciklusa nazvanog ciklus koštane pregradnje. Ovaj ciklus počinje fazom aktivacije koja uključuje mehanosenzaciju i mehanotransdukciju osteocita ili staničnim odgovorom na sistemski humoralni faktor kao što je paratireoidni hormon. Ovi startni signali potiču stvaranje specifične strukture nad koštanom površinom koju treba pregraditi i nazivamo je odjeljak koštane pregradnje (engl. bone remodeling compartment). Nadalje ovi startni signali aktiviraju osteoklastne prekursore na proliferaciju, diferencijaciju, pričvršćivanje i razgradnju određene koštane površine u sljedećoj fazi resorpcije. Nakon što se razgradi određena količina koštanog matriksa, počinje faza obrata koja uključuje oslobađanje brojnih, još uvijek nedovoljno poznatih činitelja koji povezuju razgradnju i osteoblastnu izgradnju s mineralizacijom kosti u sljedećoj fazi. Kada se stvori ista količina kosti koja se razgradila, slijedi završna faza ciklusa u kojoj se ciklus koštane pregradnje zaustavlja, a koštana površina ulazi u mirnu fazu.
Građa i oblik cirkulacijskog sustava među životinjskim vrstama bitno se razlikuju, napose u pojedinim poredbeno anatomskim aspektima, čak do neprepoznatljivost. Budući da cirkulacijski sustav ...osigurava funkcionalnu i morfološku povezanost svih dijelova organizma, njegova konstrukcija bitno ovisi o obliku organizma i njegovim biološkim osobitostima. U ovome radu, u obliku diskusije, izneseni su neki komparativno-anatomski aspekti temeljnih načela cirkulacijskog sustava u kralježnjaka.
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