Normal and Abnormal Bone Remodeling in Man

Marcus, Robert

doi:10.1146/annurev.me.38.020187.001021

Cited by 56 publications

(18 citation statements)

References 40 publications

(45 reference statements)

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“…Prolonged and local BMP-2 release is crucial for bone applications since MSC differentiation in vitro occurs between 14-21 days, 39,40 and bone formation in vivo has been reported to take place between 4-8 weeks. 41,42 Since the degradation rate of membranes is slower than the release profile of BMP-2, the release of BMP-2 is likely attributed to both degradation as well as diffusion of the growth factor out of the membrane as the charged groups of BMP-2 and HyA become screened by ionic salts in the media, weakening their interactions. Collagen molecules, which are positively charged when dissolved in 0.05 M acetic acid or pH 3.4 as prepared in this study, have a zeta potential of 51.2 -2.9 mV and decreases upon the addition of BMP-2 (46.9 -1.2 mV), which suggests that collagen molecules have a higher affinity to the highly negative anionic HyA ( -90.9 -15.6 mV) over BMP-2 proteins (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Osteogenic Potential of BMP-2-Releasing Self-Assembled Membranes

Chung

Chien

Aguado

et al. 2013

Tissue Engineering Part A

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We report here the use of novel self-assembling collagen-hyaluronic acid (HyA) membranes to deliver bone morphogenetic protein-2 (BMP-2) for orthopedic applications. Prior work has demonstrated that collagen-HyA membranes are formed initially through electrostatic interactions between the oppositely charged collagen and HyA molecules, and that membrane growth is driven by osmotic pressure imbalances between the collagen and HyA solutions. The purpose of this study was to investigate the potential of incorporating charged growth factors such as BMP-2 within the membrane for regenerative medicine applications. Membrane material properties, protein mass loss, and release kinetics of BMP-2, as well as biocompatibility and osteogenic potential in vitro and in vivo using a subcutaneous mouse model were assessed. Scanning electron microscopy and mechanical testing confirmed no loss of structural or mechanical integrity upon BMP-2 incorporation into the membranes. Slow and steady release of the growth factor was demonstrated with 17% of total loaded BMP-2 released over the course of 49 days. To test biocompatibility and osteogenic potential in vitro, human mesenchymal stem cells were cultured on collagen-HyA membranes and showed greater proliferation rates (for up to 28 days) on membranes without BMP-2, but a greater alkaline phosphatase activity and osteocalcin production on membranes releasing BMP-2. In vivo subcutaneous implantation of the membranes showed a minimal immune response with osteoblasts and mineral deposits present in the ectopic site for BMP-2-releasing membranes, further demonstrating the potential of the BMP-2-releasing membranes to induce osteogenic differentiation. This study presents a novel strategy to create self-assembled membranes using two biocompatible molecules that can deliver bioactive agents in a sustained manner to induce a local regenerative response.

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Section: Resultsmentioning

confidence: 99%

Osteogenic Potential of BMP-2-Releasing Self-Assembled Membranes

Chung

Chien

Aguado

et al. 2013

Tissue Engineering Part A

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“…3); and (5) histologically. Histologically, the microscopic changes were categorized into four main types [20][21][22][23]: G1 (bone viable, with regeneration and the presence of osteoblasts), in this category, cells were seen on the trabecular surfaces and the bone elements were clearly vital (Fig. 4); G2 (intermediate grade with higher bone viability), loss of regularity of the bone surface without uniformity in the cells of the trabecular surface with possible signs of necrosis, or intense bone remodeling, but still lacking the most complete features of viable bone; G3 (intermediate grade with minimal bone viability), the bone tissues showed clear signs of necrosis (as described above) and minimal signs of regeneration; and G4 (complete necrosis, no osteoblasts), severe, obvious bone necrosis, with well-formed or ruptured bone lamellae, surrounded by soft or necrotic myeloid tissue, or bone lamellae immersed in unfilled areas (Fig.…”

Section: Methodsmentioning

confidence: 99%

Scaphoid fracture nonunion: correlation of radiographic imaging, proximal fragment histologic viability evaluation, and estimation of viability at surgery

Bervian

Ribak

Livani

2014

International Orthopaedics (SICOT)

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Purpose The purpose of this study was to correlate the preoperative imaging, vascularity of the proximal pole, and histology of the proximal pole bone of established scaphoid fracture non-union. Methods This was a prospective non-controlled experimental study. Patients were evaluated pre-operatively for necrosis of the proximal scaphoid fragment by radiography, computed tomography (CT) and magnetic resonance imaging (MRI). Vascular status of the proximal scaphoid was determined intra-operatively, demonstrating the presence or absence of puncate bone bleeding. Samples were harvested from the proximal scaphoid fragment and sent for pathological examination. We determined the association between the imaging and intra-operative examination and histological findings. Results We evaluated 19 male patients diagnosed with scaphoid nonunion. CT evaluation showed no correlation to scaphoid proximal fragment necrosis. MRI showed marked low signal intensity on T1-weighted images that confirmed the histological diagnosis of necrosis in the proximal scaphoid fragment in all patients. Intra-operative assessment showed that 90 % of bones had absence of intra-operative puncate bone bleeding, which was confirmed necrosis by microscopic examination. Conclusions In scaphoid nonunion MRI images with marked low signal intensity on T1-weighted images and the absence of intra-operative puncate bone bleeding are strong indicatives of osteonecrosis of the proximal fragment.

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“…Infiltration of macrophages are observed within the callus in fracture repair throughout the whole process of bone remodelling. 10,11 This finding strongly suggests that the recruited macrophages are deeply involved in the bone resorption and formation; however, the precise pathophysiological functions of mononuclear cells in the normal or pathological state of bones remain undefined.…”

Section: Introductionmentioning

confidence: 99%

Identification of macrophage migration inhibitory factor in murine neonatal calvariae and osteoblasts

Onodera

Suzuki²,

Matsuno³

et al. 1996

Immunology

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SUMMARYBone resorption and formation are dynamic processes that occur in both normal and injured bone tissues. Regulation of these processes is mediated at the local level by cytokines and growth factors. Macrophage migration inhibitory factor (MIF) is one of the proinflammatory cytokines that activates macrophages and regulates production of other cytokines, such as tumour necrosis factor-a and interleukin-1. We here demonstrate, by reverse transcription-polymerase chain reaction, high expression of MIF mRNA in murine osteoblasts obtained from mouse neonatal calvariae and murine osteoblastic MC3T3-E1 cells. The presence of MIF protein in the osteoblasts was confirmed by Western blot analysis using anti-rat MIF antibody. Moreover, the immunohistochemical study revealed that MIF was localized largely in the cytoplasm. The pathophysiological function of MIF remains undefined; however, the present results suggest that MIF takes part in the osseous metabolism as well as in immunological events.

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Normal and Abnormal Bone Remodeling in Man

Cited by 56 publications

References 40 publications

Osteogenic Potential of BMP-2-Releasing Self-Assembled Membranes

Osteogenic Potential of BMP-2-Releasing Self-Assembled Membranes

Scaphoid fracture nonunion: correlation of radiographic imaging, proximal fragment histologic viability evaluation, and estimation of viability at surgery

Identification of macrophage migration inhibitory factor in murine neonatal calvariae and osteoblasts

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