Study of the healing process after transplantation of pasteurized bone grafts in rabbits.

Different bone allografts (pasteurized, autoclaved, and frozen) were compared based on their osteoinductive properties. Our primary purpose was to examine the biologic qualities of pasteurized allografts, as pasteurization inactivates most viruses transmitted by transplantation. Frozen, pasteurized, and autoclaved allografts were packed into a standard defect of rabbit ulna. The animals were sacrificed at 2 and 4 weeks after surgery. The parts of bones with experimental defects were explored en bloc, and a roentgenogram was carried out. Ulna bone samples were then embedded in methyl-methacrylate. Roentgenograms showed that after 2 weeks, calluses were well-formed, but irregular in shape in all 3 types of allografts. After 4 weeks, the calluses were regular in shape in all but the autoclaved grafts. After 2 weeks, the healing processes had begun in the frozen and pasteurized grafts, with the reaching approximately the same stage, while in the autoclaved grafts these processes were not seen and the bone particles were surrounded by connective tissue without any changes. After 4 weeks, osteoinductive processes were very strong, with the first signs of complete bone remodeling at the bone edges of the defect in pasteurized and frozen allografts. The osteoinductive values of these 2 types were very high and similar. Autoclaved allografts, on the other hand, had very low osteoinductive values, as they were still at the very beginning of the healing process. Histomorphometric analysis revealed a significant difference in both newly formed osteoid thickness and osteoblast number per microm of bone surface in all experimental groups (P &#60; 0.005). Values of osteoid thickness and osteoblast number were significantly higher in both frozen and pasteurized grafts when compared with the autoclaved ones (P &#60; 0.005). Osteogenic properties of pasteurized bone allografts were preserved, and the allografts have been gradually replaced with newly formed bone. As such, pasteurized bone grafts from a bone bank have approximately the same biologic validity as frozen grafts, while autoclaved grafts impair bone healing.</p

Hepatoregenerative role of bone morphogenetic protein-9

Bone morphogenetic protein-9 (BMP-9) is a member of the transforming growth factor beta (TGF-β) superfamily of cytokines, which regulate cell growth and differentiation during embryogenesis. Apart of that, the hypoglycemic potential of BMP-9 is of great interest. It has been confirmed that BMP-9, like insulin, improves glycemia in diabetic mice and regulates directional glucose metabolism in hepatocytes; therefore it is proposed to be a candidate hepatic insulin-sensitizing substance (HISS). In liver fibrosis, due to the portocaval shunt, insulin bypasses the organ and the liver undergoes atrophy. Parenteral administration of insulin reverses atrophy by stimulating mitogenic activity of the hepatocytes. Because BMP-9 has a signaling pathway similar to other BMPs and insulin, it is to be expected that BMP-9 has a certain regenerative role in the liver, supporting the above-mentioned is evidence of BMP-9 expression in Dissè’s spaces and BMP-7’s mitogenic activity in mucosal cells. However, further studies are needed to confirm the possible regenerative role of BMP-9

BMP signaling pathway in the rat model of TNBS colitis following BMP7 therapy

Beyond stimulating bone formation, the 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 anti- proliferative effect on experimental inflammatory bowel disease (IBD) in rat. To further investigate the BMP signaling pathway we monitored the effect of BMP7 therapy on the BMP signaling components in rat colon during different stages of experimentally induced colitis by 2, 4, 6- trinitrobenzene sulfonic acid (TNBS). The results showed increased of BMP2 and -7 expression in the chronic phase of colitis. BMP7 treatment slightly enhanced BMP4, -6 and -7, and suppressed the BMP2 expression. CTGF and noggin expression was elevated in TNBS colitis, and slightly decreased upon BMP7 therapy. BMP receptor I expression was unchanged, while BMP receptor II was increased at day 14 and 30 of TNBS inflammation, and decreased following BMP7 therapy. BMP7 increased Smad1, Smad3 and Smad4. Inhibitory Smads were increased in colitis, but not in rats treated with BMP7. We conclude that BMP signaling is preserved in colon during TNBS-induced colonic inflammation and could be modulated with BMP7, suggesting that IBD is a reversible process with self-recovery features

Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans

Bone- and cartilage-derived morphogenetic proteins (BMPs and CDMPs), which are TGFβ superfamily members, are growth and differentiation factors that have been recently isolated, cloned and biologically characterized. They are important regulators of key events in the processes of bone formation during embryogenesis, postnatal growth, remodelling and regeneration of the skeleton. In the present study, we used immunohistochemical methods to investigate the distribution of BMP-2, -3, -5, -6, -7 and CDMP-1, -2, -3 in human osteophytes (abnormal bony outgrowths) isolated from osteoarthritic hip and knee joints from patients undergoing total joint replacement surgery. All osteophytes consisted of three different areas of active bone formation: (1) endochondral bone formation within cartilage residues; (2) intramembranous bone formation within the fibrous tissue cover and (3) bone formation within bone marrow spaces. The immunohistochemistry of certain BMPs and CDMPs in each of these three different bone formation sites was determined. The results indicate that each BMP has a distinct pattern of distribution. Immunoreactivity for BMP-2 was observed in fibrous tissue matrix as well as in osteoblasts; BMP-3 was mainly present in osteoblasts; BMP-6 was restricted to young osteocytes and bone matrix; BMP-7 was observed in hypertrophic chondrocytes, osteoblasts and young osteocytes of both endochondral and intramembranous bone formation sites. CDMP-1, -2 and -3 were strongly expressed in all cartilage cells. Surprisingly, BMP-3 and -6 were found in osteoclasts at the sites of bone resorption. Since a similar distribution pattern of bone morphogenetic proteins was observed during embryonal bone development, it is suggested that osteophyte formation is regulated by the same molecular mechanism as normal bone during embryogenesis