Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid

AbstractThis study investigated the role 5-lypoxigenase (5-LO) on alveolar socket healing in aged female mice treated with zoledronic acid (ZL). Forty 129/Sv female mice (64–68 weeks old), 20 wild type (WT) and 20 5-LO knockout (5LOKO) were equally distributed according to ZL treatment: WT Control, WT ZL, 5LOKO Control, and 5LOKO ZL. ZL groups were treated with an intraperitoneal injection of 250 µg/Kg of ZL, while controls were treated with saline. Treatments were administered once a week, starting four weeks before surgery for tooth extraction and until 7 and 21 days post-surgery. Mice were euthanized for a comprehensive microscopic analysis (microCT, histomorphometry and immunohistochemistry). WT ZL mice presented intense inflammatory infiltrate (7 days), delayed bone formation (21 days), reduced collagenous matrix quality, and a deficiency in Runx-2 + , TRAP + , and macrophages as compared to controls. 5LOKO ZL animals presented decreased number of Runx-2 + cells in comparison to 5LOKO Control at 7 days, but no major changes in bone healing as compared to WT or 5LOKO mice at 21 days. The knockout of 5LO favored intramembranous bone healing in aged female mice, with a direct impact on inflammatory response and bone metabolism on the development of ONJ-like lesions.

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Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing

npj Regenerative Medicine ◽

10.1038/s41536-021-00139-x ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

S. Lee ◽

L. H. Remark ◽

A. M. Josephson ◽

K. Leclerc ◽

E. Muiños Lopez ◽

...

Keyword(s):

Wnt Signaling ◽

Notch Signaling ◽

Bone Regeneration ◽

Bone Healing ◽

Canonical Wnt Signaling ◽

Osteoprogenitor Cells ◽

Intramembranous Bone ◽

Proliferation And Differentiation ◽

Canonical Wnt ◽

Wnt Signal

AbstractAdult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.

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Collagen sponge and rhBMP-2 improve socket healing in rats treated with zoledronic acid

Brazilian Oral Research ◽

10.1590/1807-3107bor-2017.vol31.0099 ◽

2017 ◽

Vol 31 (0) ◽

Author(s):

Ji-Su OH ◽

Su-Gwan KIM

Keyword(s):

Zoledronic Acid ◽

Collagen Sponge ◽

Socket Healing

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In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms22189762 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9762

Author(s):

Junko Takahashi ◽

Shinsuke Nagasawa ◽

Motomichi Doi ◽

Masamichi Takahashi ◽

Yoshitaka Narita ◽

...

Keyword(s):

Ionizing Radiation ◽

Aminolevulinic Acid ◽

Combined Treatment ◽

Reactive Oxygen Species Generation ◽

Photodynamic Diagnosis ◽

High Dose ◽

Severe Toxicity ◽

Fractionated Radiotherapy ◽

Post Surgery

To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.

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Osteopromotion for cranioplasty

Journal of Neurosurgery ◽

10.3171/jns.1991.74.3.0487 ◽

1991 ◽

Vol 74 (3) ◽

pp. 487-491 ◽

Cited By ~ 134

Author(s):

Christer Dahlin ◽

Per Alberius ◽

Anders Linde

Keyword(s):

Bone Healing ◽

Bone Repair ◽

Slight Improvement ◽

Sprague Dawley ◽

Inner Membrane ◽

New Approach ◽

Content Type ◽

Alloplastic Materials ◽

Intramembranous Bone ◽

Sprague Dawley Rats

✓ Various techniques for treatment of large cranial defects have been reported, but the use of alloplastic materials still seems to predominate. The authors have applied and explored a new approach for bone repair which appears promising, even for use in less osteogenic environments such as the adult calvaria. Seventy-two adult Sprague-Dawley rats each received bilateral 8-mm trephine defects in the temporoparietal area; this defect size precludes spontaneous osseous healing during the lifetime of the animal. Five surgical procedures, employing various alternatives of biologically inert expanded polytetrafluoroethylene membrane positioning and intramembranous bone-chip implantation, were performed and compared to control defects. Slight improvement of bone regeneration was demonstrated with subperiosteal ectocranial and endocranial membranes, alone or in combination, and with bone chips alone or in combination with an outer or inner membrane. Virtually complete bone healing was observed in animals receiving both an outer and an inner membrane with interpositioned bone chips. The latter appeared to function primarily as space-holders by keeping the membranes separated throughout the defect. Consequently, this technique seems to significantly promote bone repair by excluding soft-tissue components from the bone-healing site.

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Platelet Derived Growth Factor Secretion and Bone Healing After Er:YAG Laser Bone Irradiation

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-09-00120.1 ◽

2011 ◽

Vol 37 (sp1) ◽

pp. 195-204 ◽

Cited By ~ 21

Author(s):

Gavriel Kesler ◽

Dana Kesler Shvero ◽

Yariv Siman Tov ◽

George Romanos

Keyword(s):

Growth Factor ◽

Laser Irradiation ◽

Bone Healing ◽

Er:Yag Laser ◽

Test Group ◽

Significant Rise ◽

Platelet Derived Growth Factor ◽

Control Group ◽

Saline Irrigation ◽

Post Surgery

Er:YAG laser irradiation has been reported to enhance wound healing. However, no studies have evaluated the synthesis of growth factors after laser irradiation. The present study investigated the effects of laser irradiation on the amount of secretion of platelet derived growth factor (PDGF) in the wound, clarifying the effects of the Er:YAG laser on the bone healing. Osteotomies were prepared in the tibiae of 28 rats using an Er:YAG laser (test group). Maximum power of 8 watts, energy per pulse of 700 mJ, and frequency up to 50 Hz were used. The laser was used with external water irrigation, a spot size of 2 mm, energy per pulse of 500 to 1000 mJ/pulse, and energy density of 32 J/cm2. Twenty eight additional rats served as a control group and their osteotomies were prepared with a drill 1.3 mm in diameter at 1000 rpm, with simultaneous saline irrigation. Two rats from the tested group and 2 from the control group were sacrificed on each day following surgery (1–14 days), and the tissue specimens were prepared for histologic evaluation. Immunohistochemical staining with anti-PDGF was performed after histologic examination. The difference between the PDGF staining intensities of the 2 treatment groups was analyzed using a multivariate logistic regression test. A significant rise in PDGF staining occurred in both groups 2–3 days following surgery. However, while high PDGF counts remained for the 2-week experimental period in the laser group, PDGF levels in the control group returned to baseline levels 8 days post surgery. The 2 groups (laser and control) were found to be different throughout the experiment, and the rat type was found to be a significant predictor (P = .000011). The present study demonstrated that Er:YAG laser irradiation seems to stimulate the secretion of PDGF in osteotomy sites in a rat model. It is possible that the high levels of PDGF are part of the mechanism that Er:YAG irradiation enhances and improves the healing of osteotomy sites.

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The Effect of Intraoperative Ferric Carboxymaltose in Joint Arthroplasty Patients: A Randomized Trial

Journal of Clinical Medicine ◽

10.3390/jcm8101674 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1674 ◽

Cited By ~ 1

Author(s):

Hee-Sun Park ◽

Tae-Yop Kim ◽

Ha-Jung Kim ◽

Young-Jin Ro ◽

Hwa-Young Jang ◽

...

Keyword(s):

Intravenous Iron ◽

Controlled Study ◽

Ferric Carboxymaltose ◽

High Dose ◽

Transfusion Rate ◽

Functional Iron Deficiency ◽

Post Surgery ◽

Total Arthroplasty ◽

Total Knee ◽

Intravenous Iron Therapy

This study assessed the efficacy of intraoperative high-dose intravenous iron therapy in facilitating recovery from postoperative anemia and reducing the transfusion rate in patients with total knee and total hip arthroplasty. This prospective randomized controlled study involved 58 subjects. Group F received 1000 mg intravenous ferric carboxymaltose and Group C received normal saline. The changes in hemoglobin (Hb), hematocrit, iron metabolism variables, transfusion rates, and the arterial partial pressure of oxygen and the fraction of oxygen (PaO2/FiO2) ratio were recorded. There were 29 patients of each group. The change in Hb levels from baseline to 1 month post-surgery was higher in Group F than in Group C (0.3 ± 1.0 g/dl vs. −0.8 ± 0.8 g/dl, p < 0.001). Functional iron deficiency occurred more frequently in Group C (0% vs. 48.3%, p < 0.001) after the operation. The incidence of postoperative anemia, transfusion rate and P/F ratio did not significantly differ between the two groups. This study suggests that intraoperative high-dose ferric carboxymaltose during lower limb total arthroplasty can facilitate the recovery from postoperative anemia. Although it could not prevent the occurrence of postoperative anemia or the administration of transfusion, this treatment seemed to overcome surgery-related decrease of iron availability.

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