Purification and characterization of a unique osteoinductive factor from bovine bone

Bentz, Hanne; Nathan, Ranga M.; Rosen, David; Armstrong, R. M.; Thompson, Andrea Y.; Segarini, Patricia R.; Mathews, M. Claravon; Dasch, James R.; Piez, Karl A.; Seyedin, Saeid M.

doi:10.1016/s0021-9258(19)47133-0

Cited by 142 publications

(7 citation statements)

References 26 publications

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“…Importantly, the actions of osteoglycin were evident in human studies, suggesting that it may provide a novel platform for development of therapies for metabolic dysfunction and the associated glycemic and skeletal complications. Osteoglycin, also known as osteoinductive factor or mimecan, is a small leucine-rich proteoglycan that is secreted into the extracellular matrix and was initially isolated from bovine bone as an inducer of matrix mineralisation [32]. It has also been shown to have a role in regulating left ventricular mass and collagen fibrillogenesis [33,34].…”

Section: Discussionmentioning

confidence: 99%

Osteoglycin, a novel coordinator of bone and glucose homeostasis

Lee

Ali

Zhang

et al. 2019

Obesity Research & Clinical Practice

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Objective: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. Methods: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies. Results: Here we identify a novel role for osteoglycin, a secreted proteoglycan, in coordinating bone accretion with changes in energy balance. Using an osteoglycin knockout mouse model, we show that at a whole body level, osteoglycin acts to suppress bone formation and modulate whole body energy supplies by altering glucose uptake through changes in insulin secretion and sensitivity, as well as by altering food intake through central signaling. Examining humans following gastric surgery as a model of negative energy balance, we show that osteoglycin is associated with BMI and lean mass as well as changes in weight, BMI, and glucose levels. Conclusions: Thus, we identify osteoglycin as a novel factor involved in the regulation of energy homeostasis and identify a role for it in facilitating the matching of bone acquisition to alterations in energy status.

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Section: Discussionmentioning

confidence: 99%

Osteoglycin, a novel coordinator of bone and glucose homeostasis

Lee

Ali

Zhang

et al. 2019

Obesity Research & Clinical Practice

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“…The components and the action mechanism of these bone inducing factors had long remained obscure. This is mainly due to the difficulties of purification of these factors and the lack of suitable in vitro bioassay systems.Recently, a number of laboratories have isolated bioactive proteins which induce cartilage and/or bone formation at the sites implanted (1,13,30,39,40). Human cDNAs for seven different bone morphogenetic proteins (BMPs), t BMP-1,…”

mentioning

confidence: 99%

“…Recently, a number of laboratories have isolated bioactive proteins which induce cartilage and/or bone formation at the sites implanted (1,13,30,39,40). Human cDNAs for seven different bone morphogenetic proteins (BMPs), t BMP-1,…”

mentioning

confidence: 99%

“…Although several bone-inducing factors were purified from bone matrix, the direct action of the isolated proteins on the osteoblastic cell lineage has not been fully investigated, except for osteogenln (37,38). Furthermore, the biological action of the factors on nonskeletal tissues has not been extensively explored; since their biological activity has been evaluated only by their in vivo implantation at ectopic sites (1,13,30,39,40,41).…”

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confidence: 99%

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Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro.

Yamaguchi

Katagiri

Ikeda

et al. 1991

The Journal of Cell Biology

689

351

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Abstract. The in vitro effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on osteogenic and myogenic differentiation was examined in two clonal cell lines of rat osteoblast-like cells at different differentiation stages, ROB-C26 (C26) and ROB-C20 (C20). The C26 is a potential osteoblast precursor cell line that is also capable of differentiating into muscle ceils and adipocytes; the C20 is a more differentiated osteoblastic cell line. Proliferation was stimulated by rhBMP-2 in C26 cells, but inhibited in C20 cells, rhBMP-2 greatly increased alkaline phosphate (ALP) activity in C26 cells, but not in C20 cells. The steady-state level of ALP mRNA was also increased by rhBMP-2 in C26 cells, but not in C20 cells. Production of 3',5'-cAMP in response to parathyroid hormone (PTH) was dose-dependently enhanced by adding rhBMP-2 in both C26 and C20 cells, though the stimulatory effect was much greater in the former. There was neither basal expression of osteocalcin mRNA nor its protein synthesis in C26 cells, but they were strikingly induced by rhBMP-2 in the presence of lot,25-dihydroxyvitamin D3. rhBMP-2 induced no appreciable changes in procollagen mRNA levels of type I and type UI in the two cell lines. Differentiation of C26 cells into myotubes was greatly inhibited by adding rhBMP-2. The inhibitory effect of rhBMP-2 on myogenic differentiation was also observed in clonal rat skeletal myoblasts (L6). Like BMP-2, TGF-fll inhibited myogenic differentiation. However, unlike BMP-2, TGF-fll decreased ALP activity in both C26 and C20 cells. TGF-/$1 induced neither PTH responsiveness nor osteocalcin production in C26 cells, but it increased PTH responsiveness in C20 cells. These results clearly indicate that rhBMP-2 is involved, at least in vitro, not only in inducing differentiation of osteoblast precursor cells into more mature osteoblast-like cells, but also in inhibiting myogenic differentiation.CTOPIC bone formation is elicited at intramuscular sites by implantation of bone inducing factors contained in demineralized bone matrix (28,35,36). This indicates that cells of the osteoblast lineage have a close relationship with those of the muscular lineage in their ontogeny, and the development of the two cell lineages may be mutually regulated by some factor(s) stored in bone matrix. The components and the action mechanism of these bone inducing factors had long remained obscure. This is mainly due to the difficulties of purification of these factors and the lack of suitable in vitro bioassay systems.Recently, a number of laboratories have isolated bioactive proteins which induce cartilage and/or bone formation at the sites implanted (1,13,30,39,40). Human cDNAs for seven different bone morphogenetic proteins (BMPs), t BMP-1, BMP-5, BMP-6 (Vgr-1 [141), and BMP-7 (OP-1125, 30]) have been cloned (41,42). The sequences deduced from these cDNAs have indicated that BMP-2 through BMP-7 are members of transforming growth factorfl (TGF-fl) superfamily (14,25,41,42). Furthermore, active recombinant human bone mor...

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“…Several laboratories have reported the isolation of factors from demineralized bone matrix (DBM) that could induce bone formation, such as bone morphogenetic protein, osteogenin 3 and osteoinductive factor. 4 In addition, genes of the bone-inductive molecules BMP-1, BMP-2A, BMP-2B, and BMP-3 have been cloned. 5 A third mechanism of ossification, termed transchondroid bone formation, has also been described.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of New Autologous Biomaterials into Jaw Cleft

et al. 2001

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This study compared bone-marrow grafting using chondroid or fibula bone grafts transplanted into simulated alveolar bone defects in mice. The osteogenic procedure was also investigated. As an experimental model of the maxillary alveolar bone cleft, suitable for testing bone-inductive materials, a surgical trephine with a low-speed dental engine was used to form critical-sized defects in the pre-maxillary bones of male mice. Distraction osteogenesis was performed using an external fixation device. The osteotomy site was surrounded by an external callus, consisting of hyaline cartilage, that contained a large quantity of chondroid bone. Transplanted bone within chondroid bone was characterized by bone formation and remodelling 30 days post-transplantation, and bone adhesion following chondroid bone grafting was better than adhesion following fibula grafting. The present findings are the first to demonstrate the potential of chondroid bone transplantation as a new therapeutic system of bone grafting, suitable for bone substitution in craniofacial bone defects.

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Purification and characterization of a unique osteoinductive factor from bovine bone

Cited by 142 publications

References 26 publications

Osteoglycin, a novel coordinator of bone and glucose homeostasis

Osteoglycin, a novel coordinator of bone and glucose homeostasis

Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro.

Transplantation of New Autologous Biomaterials into Jaw Cleft

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