In vivo analysis of the half-life of the osteoinductive potential of demineralized bone matrix using diffusion chambers

Landesman, Richard; Reddi, A. Hari

doi:10.1007/bf02556005

Cited by 20 publications

(9 citation statements)

References 12 publications

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“…Based on the long-duration acid demineralization data (C90 min), we estimated that the diffusion halflife of BMP-7 from the DBM was approximately 26 h. Landesman and Reddi (Landesman and Reddi 1989) suggested a soluble factor from DBM was associated with osteoinduction and presented evidence that after an initial in vivo latent period, the osteoinductive potential of the DBM had a half-life of five to 7 days. There was, however, little similarity between their study and ours, so the two half-lives cannot be directly compared.…”

Section: Discussionmentioning

confidence: 99%

BMP depletion occurs during prolonged acid demineralization of bone: characterization and implications for graft preparation

et al. 2009

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Demineralization of allograft bone increases the bioavailability of matrix-associated bone morphogenetic proteins (BMPs), rendering these grafts osteoinductive. While osteoinductivity is related to BMP content, little is known about how the demineralization protocol, in particular, extended demineralization times, affects graft BMP levels. We characterized the BMP-7 content of <710 μm bovine bone powder demineralized under various conditions. Using 1 g of bone per 50 ml of 0.125 N, 0.25 N, or 0.5 N HCl, demineralization was performed at room temperature for 5 min to 24 h. Minimum residual calcium levels were obtained within 90 min and were <1 wt % using the 0.25 N and 0.5 N baths and 17 wt % using the 0.125 N bath. Measured peak BMP-7 levels were also obtained within 90 min and were 161-165 ng g(-1) using the 0.25 N and 0.5 N baths and 55.2 ng g(-1) using the 0.125 N bath. This compares to 5.1 ng g(-1) for undemineralized bone. Further acid bath exposure to 24 h resulted in BMP-7 decline to about 50% of the peak value, which was significant. The BMP-7 half-life was estimated to be 26 h. It is likely that the decline was due to diffusion of BMP-7 from the bone matrix into the acid. These results suggest the importance of not over demineralizing bone grafts and should stimulate further research that can be incorporated into the processing methodology followed by tissue banks.

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Section: Discussionmentioning

confidence: 99%

BMP depletion occurs during prolonged acid demineralization of bone: characterization and implications for graft preparation

et al. 2009

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“…Though the cellular events by which OG induces bone regeneration remain to be elucidated, the study presented here indicates that cellular effects are manifest as early as 3 days after treatment and persist beyond 70 days. As the biological half-life of the bone-inductive potential of demineralized bone matrix powder was estimated to be 5-7 days [30], it would be important to develop a system that delivers bone-inductive proteins within a 1 to 7-day window. Whereas the present study involved defects that were treated immediately, it remains to be shown how delay of treatment might diminish the bone-inductive response.…”

Section: Discussionmentioning

confidence: 99%

Temporal changes during bone regeneration in the calvarium induced by osteogenin

et al. 1993

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Repair of rat craniotomy defects, 8 mm in diameter, was compared with that of defects treated with either rat insoluble collagenous bone matrix (ICBM) or partially purified bovine osteogenin, a bone-inductive protein, reconstituted with ICBM (OG/ICBM). Repair of all defects was similar histologically throughout the first 3 days, characterized by acute, then chronic inflammation and granulation tissue formation. In defects treated with OG/ICBM, cartilage and osteoblasts were present at day 5. By day 9, cartilage and osteoid production were active. New bone showed hematopoietic tissue by day 11; a complete bone bridge was established by day 21. By day 42, fatty marrow was present. Defects treated with ICBM alone showed islands of cartilage and bone embedded in connective tissue at day 9, which reached peak maturity by day 14. In these and in untreated defects, significant osteoblastic and osteoclastic activity, located primarily at the margins of the defects, subsided by day 28. Untreated defects gradually filed in with fibrous connective tissue which matured throughout 156 days. Radiopacity, quantified by computerized image analysis, increased significantly between days 9 and 11 in OG/ICBM-treated defects, and remained greater (P < 0.05) than that of the ICBM-treated defects. There was a more gradual increase in radiopacity in ICBM-treated defects. The sequence of morphologic events during calvarial bone regeneration was very similar to that described previously for heterotopic bone formation induced by demineralized bone matrix.

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“…One might suspect that increased granulocyte would degrade the BMP-2 and result in impaired bone formation (Landesman and Reddi, 1989). However, this hypothesis appears unlikely.…”

Section: Kuwabara Et Almentioning

confidence: 99%

Overexpression of the Granulocyte Colony-Stimulating Factor Gene Impairs Bone Morphogenetic Protein Responsiveness in Mice

Kuwabara

Wada

Oda

et al. 2001

Laboratory Investigation

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SUMMARY:Granulocyte colony-stimulating factor (G-CSF) is the major hematopoietic growth factor regulating the production and differentiation of neutrophils. We previously demonstrated that permanent overexpression of G-CSF in transgenic mice produces a dramatic enlargement of the bone cavity and reduction of bone mass. This phenotype was shown to be associated with an increase of osteoclast-mediated bone resorption. As a way of determining the role of G-CSF in bone formation in vivo, an ectopic bone was induced subcutaneously into G-CSF transgenic mice by bone morphogenetic protein (BMP)-2, a potent initiator of bone and cartilage from undifferentiated mesenchymal cells. A BMP-2/atelocollagen pellet containing recombinant human BMP-2 was implanted into a dorsal subfascial pocket. At one week after implantation, proliferation of mesenchymal cells around the implant was significantly decreased in transgenic mice compared with control mice. At three weeks, an ectopic bone containing bone marrow was formed both in transgenic and control mice. However, the ectopic bones of the transgenic mice were smaller and less consistent than those of control mice, and the calcium contents were reduced to 56.2% of those of controls. The ectopic bone in the G-CSF mice showed poor development of both lamellar and trabecular bone. Semiquantitative reverse transcription-polymerase chain reaction analysis of the ectopic bone at 3 weeks disclosed no significant differences in the mRNA levels of type I collagen, osteopontin, and osteocalcin between G-CSF mice and control mice. Immunohistochemical study in G-CSF mice showed reduced staining of osteocalcin in the bone matrix surrounding the reduced number of osteoblasts. The half-life of BMP in the implants was prolonged to 7 to 9 days in the G-CSF mice, whereas it was 5 days in the control mice. Collectively, the permanent expression of G-CSF may retard the differentiation process of osteoblasts by impairing the initial induction of mesenchymal cells, resulting in reduction of bone mass, suggesting that G-CSF regulates the bone metabolism by modulating both osteoclast and osteoblast function. Furthermore, it is suggested that G-CSF is a potent modulator of the BMP-2

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In vivo analysis of the half-life of the osteoinductive potential of demineralized bone matrix using diffusion chambers

Cited by 20 publications

References 12 publications

BMP depletion occurs during prolonged acid demineralization of bone: characterization and implications for graft preparation

BMP depletion occurs during prolonged acid demineralization of bone: characterization and implications for graft preparation

Temporal changes during bone regeneration in the calvarium induced by osteogenin

Overexpression of the Granulocyte Colony-Stimulating Factor Gene Impairs Bone Morphogenetic Protein Responsiveness in Mice

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