scholarly journals Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Structure ◽  
Precursor Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

CO-ADMINISTRATION OF SYSTEMIC ZOLEDRONATE PROMOTES OSTEOGENESIS INDUCED BY A LOCAL CO-DELIVERY OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 AND β-TRICALCIUM PHOSPHATE IN THE BONE MARROW OF THE RABBIT FEMUR

2016 ◽  
Vol 19 (03) ◽  
pp. 1650015
Author(s):  
Kenji Mamoto ◽  
Yoichi Ohta ◽  
Koichi Ichikawa ◽  
Yuuki Imai ◽  
Yukihide Minoda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Morphogenetic Proteins ◽  
Tricalcium Phosphate ◽  
Bone Structure ◽  
Rabbit Model ◽  
Volume Ratio ◽  
Bone Morphogenetic Protein 2 ◽  
Histological Evaluation ◽  
Micro Computed Tomography ◽  
Left Femur

Purpose: Bone morphogenetic proteins (BMPs) strongly induce osteogenesis. However, BMPs also directly or indirectly stimulate catabolic osteoclast activity, leading to strong bone resorption, especially in the bone marrow. The aim of this study was to investigate whether the combination of a local recombinant human BMP-2 (rh-BMP-2)/beta-tricalcium phosphate ([Formula: see text]-TCP) composite with systemically administrated bisphosphonate, zoledronate (ZOL) could promote osteogenesis in a rabbit model. Methods: [Formula: see text]-TCP columns, with or without rh-BMP-2 (30 [Formula: see text]g/column), were implanted into the left femur canal of 20 rabbits. The animals were injected with 0.4[Formula: see text]mg of ZOL or saline 1 week after implantation. The implants were evaluated by micro-computed tomography ([Formula: see text]-CT) and histology 6 weeks after implantation. Results: [Formula: see text]-CT data revealed that the bone volume/tissue volume ratio of bone nodules inside [Formula: see text]-TCP columns in combination with rh-BMP-2 and ZOL was significantly higher than that of [Formula: see text]-TCP columns treated with rh-BMP-2, ZOL, or neither. Histological evaluation also revealed that significantly more new bone formed inside [Formula: see text]-TCP columns treated with rh-BMP-2 and ZOL than inside [Formula: see text]-TCP columns treated with rh-BMP-2, ZOL, or neither. Conclusion: This combination therapy contributed to the maintenance of the newly formed BMP-2-induced bone structure in the bone marrow.

scholarly journals Association of Antibiotic Alterations in Gut Microbiota With Decreased Osseointegration of an Intramedullary Nail in Mice With and Without Osteomyelitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingqi Zhao ◽  
Zhaohui Zhang ◽  
Yiran Wang ◽  
Kai Qian ◽  
Hanjun Qin ◽  
...  
Keyword(s):  
Bone Formation ◽  
Gut Microbiota ◽  
Bone Mass ◽  
Proinflammatory Cytokines ◽  
Intramedullary Nail ◽  
Bone Structure ◽  
Tartrate Resistant Acid Phosphatase ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Marrow Cavity

Treatment of osteomyelitis requires prolonged antibiotic therapy which significantly alters the gut microbiota. While the influences on bone mass and microstructure have been extensively studied, it is poorly understood what impact the changes in gut microbiota may have on the host response to osseointegration around an intramedullary nail implanted. Here, we explored the influence of gut microbiota on the bone osseointegration process around an implant under two conditions: implantation of an intramedullary nail in the bone marrow cavity and chronic osteomyelitis (CO) induced by Staphylococcus aureus infection. Body weight, hepatorenal functions, serum levels of proinflammatory cytokines were monitored. The composition of gut microbiota was assessed via 16S rRNA sequencing, and the bone condition was analyzed via micro-computed tomography, hematoxylin and eosin staining, Safranin O-fast green and Goldner’s trichrome staining. Osteoblastogenesis and osteoclastogenesis were assessed by detecting tartrate-resistant acid phosphatase and osterix expression. We found that perturbation of gut microbiota (increase in Proteobacteria and decrease in Bacteroidetes) associated with delayed osseointegration and increased levels of proinflammatory cytokines in the serum (p&lt;0.05), lower bone mass (p&lt;0.05), deficient endochondral ossification and bone formation, reduced osteoblastogenesis (p&lt;0.05) and enhanced osteoclastogenesis (p&lt;0.001). Survival rates (p=0.002) and bacterial loads (p=0.0363) in bone differed significantly between the CO and antibiotic-treated CO mice, but cytokines levels, bone mineral density, and bone formation did not differ, likely because of the severely damaged bone structure. In summary, antibiotic treatment perturbed the gut microbiota and significantly interfered with the bone osseointegration around the nail by increasing proinflammatory cytokine levels in circulation, inhibiting osteoblastogenesis, enhancing osteoclastogenesis, and thus leading to higher pathogen colonization as well as higher mortality postinfection. This report of ours is the first to demonstrate antibiotic-induced alterations in the gut microbiota affect bone osseointegration, helping us understand the role of gut microbiota disorders in osteoblastogenesis and osteoclastogenesis following implant insertion with or without infection.

scholarly journals Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments

2020 ◽  
Vol 21 (21) ◽  
pp. 7967
Author(s):  
Shuji Nosho ◽  
Ikue Tosa ◽  
Mitsuaki Ono ◽  
Emilio Satoshi Hara ◽  
Kei Ishibashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Marrow Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Other Hand

Bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) have been regarded as the major cytokines promoting bone formation, however, several studies have reported unexpected results with failure of bone formation or bone resorption of these growth factors. In this study, BMP-2 and FGF-2 adsorbed into atellocollagen sponges were transplanted into bone defects in the bone marrow-scarce calvaria (extramedullary environment) and bone marrow-abundant femur (medullary environment) for analysis of their in vivo effects not only on osteoblasts, osteoclasts but also on bone marrow cells. The results showed that BMP-2 induced high bone formation in the bone marrow-scarce calvaria, but induced bone resorption in the bone marrow-abundant femurs. On the other hand, FGF-2 showed opposite effects compared to those of BMP-2. Analysis of cellular dynamics revealed numerous osteoblasts and osteoclasts present in the newly-formed bone induced by BMP-2 in calvaria, but none were seen in either control or FGF-2-transplanted groups. On the other hand, in the femur, numerous osteoclasts were observed in the vicinity of the BMP-2 pellet, while a great number of osteoblasts were seen near the FGF-2 pellets or in the control group. Of note, FCM analysis showed that both BMP-2 and FGF-2 administrated in the femur did not significantly affect the hematopoietic cell population, indicating a relatively safe application of the two growth factors. Together, these results indicate that BMP-2 could be suitable for application in extramedullary bone regeneration, whereas FGF-2 could be suitable for application in medullary bone regeneration.

scholarly journals New Bone Formation in Tuberculous-Infected Vertebral Body Defect after Administration of Bone Marrow Stromal Cells in Rabbit Model

2016 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
Ahmad Jabir Rahyussalim ◽  
Tri Kurniawati ◽  
Nurjati Chairani Siregar ◽  
Agus Syahrurachman ◽  
Ismail Hadisubroto Dilogo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Vertebral Body ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Rabbit Model ◽  
Marrow Stromal Cells ◽  
New Bone Formation

scholarly journals Autoradiographic Study on the Origin and Fate of Small Lymphoid Cells in the Dog Bone Marrow: Effect of Femoral Artery Clamping during in Vivo Availability of H3-Thymidine

Blood ◽  
1964 ◽  
Vol 24 (3) ◽  
pp. 254-266 ◽  
Author(s):  
G. KEISER ◽  
H. COTTIER ◽  
N. ODARTCHENKO ◽  
V. P. BOND
Keyword(s):  
Bone Marrow ◽  
Femoral Artery ◽  
Blood Stream ◽  
Autoradiographic Study ◽  
Precursor Cells ◽  
Lymphoid Cells ◽  
The Other ◽  
Dog Bone ◽  
Two Populations

Abstract The origin and fate of small lymphoid cells in the dog bone marrow were studied autoradiographically by observing the effect of clamping of the femoral artery during in vivo availability of H3-thymidine. Heavily labeled small lymphoid cells appeared in the bone marrow of the clamped leg 3 hours after injection of the tracer and increased in number up to 6 days. The labeling indices of these cells, however, were significantly lower than those of control marrow. A possible interpretation is that dog bone marrow contains two populations of small lymphoid cells, one migrating into the marrow via the blood stream, the other originating from local precursor cells within the marrow. There was no evidence for a transformation of migrated small lymphoid cells into erythroblasts during the first 48 hours after injection of H3-thymidine.

scholarly journals Cortical bone dynamics, strength, and densitometry after induction of emphysema in hamsters

2003 ◽  
Vol 95 (2) ◽  
pp. 631-634 ◽  
Author(s):  
Jill E. Shea ◽  
Scott C. Miller ◽  
David C. Poole ◽  
John P. Mattson
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Bone Formation ◽  
Cortical Bone ◽  
Pulmonary Disease ◽  
Bone Mineral ◽  
Bone Structure ◽  
Chronic Obstructive ◽  
Pathophysiological Mechanism ◽  
Mineral Density ◽  
Obstructive Pulmonary Disease

Recent evidence suggests that patients suffering from chronic obstructive pulmonary disease are also at an increased risk of developing osteoporosis. The pathophysiological mechanism(s) linking these progressive diseases is unknown. The goal of this investigation was to determine whether there were alterations in bone mineral density and content, cortical bone structure and strength, and indexes of bone formation and resorption in the elastase-induced emphysematous hamster. At 3 wk after induction of emphysema, the femoral bone mineral content was 8% less ( P = 0.026) and the femoral fracture strength was 6% less ( P = 0.032) in the emphysematous hamster than in controls. The cortical area was 8.4% less ( P = 0.013) and the periosteal mineral appositional rate was 27% less ( P = 0.05) than in controls. Additionally, the endocortical eroded surface in the emphysematous group was about twice that in the control group ( P = 0.003). Differences in some indexes of bone formation and resorption, paralleled by differences in bone structure and strength, were observed 3 wk after induction of emphysema. These differences in skeletal metabolism and strength may help explain some of the skeletal changes associated with chronic obstructive pulmonary disease in humans.

The Effect of Graft Pretensioning on Bone Tunnel Diameter and Bone Formation After Anterior Cruciate Ligament Reconstruction in a Rat Model: Evaluation With Micro–Computed Tomography

2017 ◽  
Vol 45 (6) ◽  
pp. 1349-1358 ◽  
Author(s):  
Jian-Chun Zong ◽  
Richard Ma ◽  
Hongsheng Wang ◽  
Guang-Ting Cong ◽  
Amir Lebaschi ◽  
...  
Keyword(s):  
Bone Formation ◽  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Bone Tunnel ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Load To Failure ◽  
Tunnel Diameter ◽  
Anterior Cruciate ◽  
Bone Tunnels

Background: Moderate graft pretensioning in anterior cruciate ligament (ACL) reconstruction is paramount to restore knee stability and normalize knee kinematics. However, little is known about the effect of graft pretensioning on graft-to-bone healing after ACL reconstruction. Hypothesis: Moderate graft pretensioning will improve bone formation within the bone tunnel after ACL reconstruction, resulting in superior load to failure. Study Design: Controlled laboratory study. Methods: 67 male Sprague-Dawley rats underwent unilateral ACL reconstruction with a flexor digitorum longus tendon autograft. The graft was subjected to pretensioning forces of 0 N, 5 N, or 10 N. Custom-made external fixators were used for knee immobilization postoperatively. Rats were euthanized for biomechanical load-to-failure testing (n = 45) and micro–computed tomography (μCT) examination (n = 22) at 3 and 6 weeks after surgery. Three regions of each femoral and tibial bone tunnel (aperture, middle, and tunnel exit) were chosen for measurement of tunnel diameter and new bone formation. Results: Biomechanical tests revealed significantly higher load-to-failure in the 5-N graft pretensioned group compared with the 0- and 10-N groups at 3 weeks (8.58 ± 2.67 N vs 3.96 ± 1.83 N and 4.46 ± 2.62 N, respectively) and 6 weeks (16.56 ± 3.50 N vs 10.82 ± 1.97 N and 7.35 ± 2.85 N, respectively) after surgery ( P < .05). The mean bone tunnel diameters at each of the 3 regions were significantly smaller in the 5-N group, at both the femoral and tibial tunnel sites, than in the 0- and 10-N groups ( P < .05). At 3 and 6 weeks postoperatively, the bone mineral density, bone volume fraction, and connectivity density around the aperture and middle regions of the tibial bone tunnels were all significantly higher in the 5-N group compared with the 0- and 10-N groups ( P < .05). In the aperture and middle regions of the femoral bone tunnels, pretensioning at either 5 or 10 N resulted in increased bone formation compared with the nonpretensioned group at 3 weeks postoperatively. No differences were found in bone formation between any of the 3 femoral tunnel regions at 6 weeks. Conclusion: Graft pretensioning can stimulate new bone formation and improve tendon-to-bone tunnel healing after ACL reconstruction. Clinical Relevance: Optimal graft pretensioning force in ACL reconstruction can improve bone tunnel healing. Further study is necessary to understand the mechanisms underlying the effect of graft pretensioning on healing at the bone-tunnel interface.

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