Teriparatide attenuates scarring around murine cranial bone allograft via modulation of angiogenesis

Yakubovich, Doron Cohn; Eliav, Uzi; Yalon, Eran; Schary, Yeshai; Sheyn, Dmitriy; Sun, Shuting; McKenna, Charles E.; Lev, Shaya; Binshtok, Alexander M.; Pelled, Gadi; Gazit, Dan; Gazit, Zulma

doi:10.1016/j.bone.2017.01.020

Cited by 18 publications

(20 citation statements)

References 55 publications

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“…Moreover, teriparatide modulates angiogenesis in bone allografts, resulting in a higher number of blood capillaries, and, simultaneously, narrows blood vessel diameters, indicating a matured capillary network. 97 These findings support the view that PTH stimulates the process of bone regeneration by inducing new blood vessel formation.…”

Section: Systemic Pharmacological Treatmentsupporting

confidence: 74%

Vascularization Strategies in the Prevention of Nonunion Formation

Menger

Laschke

Orth

et al. 2021

Tissue Engineering Part B: Reviews

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Delayed healing and nonunion formation are major challenges in orthopedic surgery, which require the development of novel treatment strategies. Vascularization is considered one of the major prerequisites for successful bone healing, providing an adequate nutrient supply and allowing the infiltration of progenitor cells to the fracture site. Hence, during the last decade, a considerable number of studies have focused on the evaluation of vascularization strategies to prevent or to treat nonunion formation. These involve (1) biophysical applications, (2) systemic pharmacological interventions, and (3) tissue engineering, including sophisticated scaffold materials, local growth factor delivery systems, cell-based techniques, and surgical vascularization approaches. Accumulating evidence indicates that in nonunions, these strategies are indeed capable of improving the process of bone healing. The major challenge for the future will now be the translation of these strategies into clinical practice to make them accessible for the majority of patients. If this succeeds, these vascularization strategies may markedly reduce the incidence of nonunion formation.

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Section: Systemic Pharmacological Treatmentsupporting

confidence: 74%

Vascularization Strategies in the Prevention of Nonunion Formation

Menger

Laschke

Orth

et al. 2021

Tissue Engineering Part B: Reviews

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“…Cells were transduced with a Lentiviral vector encoding for Luciferase2 (Luc2) reporter gene to allow for in vivo tracking, as previously reported [31][32][33][34] and characterized for their marker expression, differentiation potential, and risk of cellular transformation. For in vivo evaluation, a 5-mm round calvarial critical size defect was created in immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice (NOD.CB17-Prkdcscid/NCrHsd, Envigo) as previously reported 35,36 and the following three experimental groups were implanted in a randomized fashion: (a) decellularized allografts only, (b) decellularized allografts seeded with BM-MSC-Luc2, and (c) decellularized allografts seeded with iNCC-MPC-Luc2. Animals were monitored for a duration of 8 weeks postsurgery: BLI was performed to monitor cell viability at the defect site and μCT was done to evaluate the quantity and quality of new bone formation.…”

Section: Experimental Designmentioning

confidence: 99%

“…Animal surgeries were performed in accordance to the approved IACUC protocol #007961 "Bone regeneration using stem cells in a mouse model," as previously reported. 35,36 To create calvarial defects, the 8-week-old NOD/SCID mice were anesthetized by an intraperitoneal (IP) injection of ketamine/dexmedetomidine (75 mg/1 mg/kg, IP injection). Buprenorphine (0.05 mg/kg) was subcutaneously (SQ) injected for pain control.…”

Section: Calvarial Defect Repairmentioning

confidence: 99%

Neural crest-derived mesenchymal progenitor cells enhance cranial allograft integration

Glaeser

Behrens

Stefanovic

et al. 2021

Stem Cells Translational Medicine

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Replacement of lost cranial bone (partly mesodermal and partly neural crest‐derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow‐derived mesenchymal stromal cells (mesoderm‐derived BM‐MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) improves implant‐to‐bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC‐MPCs. BM‐MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (μCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC‐MPC‐Luc2 vs BM‐MSC‐Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, μCT analysis showed enhanced structural parameters in the iNCC‐MPC‐Luc2 group and increased bone volume in the BM‐MSC‐Luc2 group compared to controls. Histology demonstrated improved integration of iNCC‐MPC‐Luc2 allografts compared to BM‐MSC‐Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft‐host interphase in cell‐seeded groups. The iNCC‐MPC‐Luc2 group also demonstrated improved biomechanical properties compared to BM‐MSC‐Luc2 implants and cell‐free controls. Our results show an improved integration of iNCC‐MPC‐Luc2‐coated allografts compared to BM‐MSC‐Luc2 and controls, suggesting the use of iNCC‐MPCs as potential cell source for cranial bone repair.

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“…As reported by Marques et al (2009), teriparatide down-regulates the expression and activation of bone resorption biomarkers, such as interleukin-6, MMP-2, and MMP-9 that are responsible for bone resorption, reducing the number of mature osteoclasts. Subsequent animal studies included in this review confirmed the benefits of systematic administration of teriparatide in rat calvarial defects, showing significant increase of bone regeneration (Andreassen and Cacciafesta, 2004;Cohn Yakubovich et al, 2017;Park et al, 2019;Staconven et al, 2013;Yoshida et al, 2019;Yun et al, 2010). Teriparatide may enhance periodontal healing as demonstrated by higher number of PCNA-and VEGF-positive cells, and increased osterix expression, thus promoting PDL cell proliferation, angiogenesis, and osteoblast differentiation (Yoshida et al, 2019).…”

Section: Discussionmentioning

confidence: 61%

The role of bone anabolic drugs in the management of periodontitis: a scoping review

Cecoro¹,

Paoletta²,

Annunziata³

et al. 2021

eCM

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The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.

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Teriparatide attenuates scarring around murine cranial bone allograft via modulation of angiogenesis

Cited by 18 publications

References 55 publications

Vascularization Strategies in the Prevention of Nonunion Formation

Vascularization Strategies in the Prevention of Nonunion Formation

Neural crest-derived mesenchymal progenitor cells enhance cranial allograft integration

The role of bone anabolic drugs in the management of periodontitis: a scoping review

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