Osteoblast Response to Titanium Surfaces Coated with Strontium Ranelate–Loaded Chitosan Film

Tian, Ai Hua; Zhai, Jun-Jiang; Yan, Ping; Zhang, Li; Teng, Min-hua; Liao, Jian; Sun, Xu; Lü, Xing

doi:10.11607/jomi.3806

Cited by 19 publications

(30 citation statements)

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“…Our gene expression data showed SrHAn double activity on OBs and OCs. Several studies reported that strontium modulates alkaline phosphatase (ALP) activity and Runx-2 expression (Tian et al, 2014) in OBs and OBs progenitors while promoting Wnt/β-catenin pathway in human bone marrow derived mesenchymal stem cells (MSCs), thereby enhancing ECM secretion and osteogenic differentiation (Yang et al, 2011). Interestingly, in our study no significant variation was detected in Runx2 levels.…”

Section: Discussioncontrasting

confidence: 51%

“…Compelling experimental results showed the efficacy of strontium cations, as osteoinductive and anti-osteoporotic agents (Rohnke et al, 2016;Carmo et al, 2018;Li et al, 2018). Strontium modulates bone remodeling by enhancing bone formation and suppressing bone resorption (Chattopadhyay et al, 2006;Takaoka et al, 2010;Yang et al, 2011;Saidak and Marie, 2012;Tian et al, 2014) although, to date, the molecular and cellular mechanisms of strontium activity remain partially elusive. Physical-chemical properties of strontium-substituted hydroxyapatite nanoparticles in combination with calcium hydroxyapatite nanoparticles and their in vitro osteoinductivity were assessed in our previous works (Frasnelli et al, 2016;Visai et al, 2017;Cristofaro et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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An in vivo Comparison Study Between Strontium Nanoparticles and rhBMP2

Montagna

Cristofaro

Fassina

et al. 2020

Front. Bioeng. Biotechnol.

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The osteoinductive property of strontium was repeatedly proven in the last decades. Compelling in vitro data demonstrated that strontium hydroxyapatite nanoparticles exert a dual action, by promoting osteoblasts-driven matrix secretion and inhibiting osteoclasts-driven matrix resorption. Recombinant human bone morphogenetic protein 2 (rhBMP2) is a powerful osteoinductive biologic, used for the treatment of vertebral fractures and critically-sized bone defects. Although effective, the use of rhBMP2 has limitations due its recombinant morphogen nature. In this study, we examined the comparison between two osteoinductive agents: rhBMP2 and the innovative strontium-substituted hydroxyapatite nanoparticles. To test their effectiveness, we independently loaded Gelfoam sponges with the two osteoinductive agents and used the sponges as agent-carriers. Gelfoam are FDA-approved biodegradable medical devices used as delivery system for musculoskeletal defects. Their porous structure and spongy morphology make them attractive in orthopedic field. The abiotic characterization of the loaded sponges, involving ion release pattern and structure investigation, was followed by in vivo implantation onto the periosteum of healthy mice and comparison of the effects induced by each implant was performed. Abiotic analysis demonstrated that strontium was continuously released from the sponges over 28 days with a pattern similar to rhBMP2. Histological observations and gene expression analysis showed stronger endochondral ossification elicited by strontium compared to rhBMP2. Osteoclast activity was more inhibited by strontium than by rhBMP2. These results demonstrated the use of sponges loaded with strontium nanoparticles as potential bone grafts might provide better outcomes for complex fractures. Strontium nanoparticles are a novel and effective non-biologic treatment for bone injuries and can be used as novel powerful therapeutics for bone regeneration.

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Section: Discussioncontrasting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

An in vivo Comparison Study Between Strontium Nanoparticles and rhBMP2

Montagna

Cristofaro

Fassina

et al. 2020

Front. Bioeng. Biotechnol.

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“…Locally application drug could accelerate this procedure to reach the sufficient osseointegration earlier, which is more time saving and effective than osteoporosis treatment. Tian and Nair uploaded SrR on some biomaterial to achieve the local delivery of SrR, and all got a good result of bone regeneration26,27. Nevertheless, questions about the effectiveness and safety of SrR local delivery have been raised.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent Effects of Strontium Ranelate on Ovariectomy Rat Bone Marrow Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells

Guo¹,

Wei²,

Lu³

et al. 2016

Int. J. Biol. Sci.

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In clinic, strontium ranelate (SrR) is a useful drug to treat osteoporosis by orally taken method, but some side effect appeared in recent years. The aim of this study is to evaluate the effectiveness and safety of SrR on cells by direct application, to study the possibility of local application of this drug. Qualitative ALP staining, quantitative ALP activity assay, alizarin red staining, realtime PCR and westernblot assay were used to evaluate the osteogenesis ability of SrR under normal or osteogenic induction environment of ovariectomy bone marrow mesenchymal stem cells (OVX-BMSCs). The angiogenesis ability of SrR was studied by immunofluorescence staining of CD31 and vWF of OVX-BMSCs under angiogenesis induction environment, transwell, tubeformation and realtime PCR assay of HUVECs. Signaling pathway of PI3K/AKT/mTOR was also studied. The result demonstrated that SrR could enhance proliferation and osteogenic differentiation of OVX-BMSCs. The osteogenesis effect of SrR has been proved by the better performed of ALP activity, alizarin red staining and the remarkable up-regulation of ALP, Col-I, Runx2, OCN, BMP-2, BSP, OPG of the OVX-BMSCs, and reduction of RANKL. In addition, SrR promotes angiogenesis differentiation of both OVX-BMSCs and HUVECs. Higher intensity of immunostaining of CD31 and vWF, better result of transwell and tubeformation assay could be observed in SrR treated group, and increasing mRNA levels of VEGF and Ang-1 in the OVX-BMSCs, VEGF in HUVECs were learnt. Signaling pathway assay showed that PI3K/AKT/mTOR signaling pathway was involved in this SrR triggered angiogenesis procedure. The thrombosis marker ET-1, PAI-1 and t-PA were up-regulated, but no significant differences for low concentration (<0.5mM). The concentration between 0.25-0.5mM may be more appropriate for local application, and locally application of SrR could be considered as a promising way for bone regeneration.

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“…Topical application of SR is a potential way to minimize these effects (49). Prostheses coated with SR may be able to inhibit aseptic loosening (50,51).…”

Section: Discussionmentioning

confidence: 99%

Effects of strontium ranelate on wear particle‑induced aseptic loosening in female ovariectomized mice

et al. 2018

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Aseptic loosening and menopause‑induced osteoporosis are caused by an imbalance between bone formation and osteolysis. With an aging population, the probability of simultaneous occurrence of such conditions in an elderly individual is increasing. Strontium ranelate (SR) is an anti‑osteoporosis drug that promotes bone formation and inhibits osteolysis. The present study compared the effects of SR with those of the traditional anti‑osteoporosis drug alendronate (ALN) using an ovariectomized mouse model of osteolysis. The degree of firmness of the prosthesis and the surrounding tissue was examined, a micro‑CT scan of the prosthesis and the surrounding tissue was performed, and the levels of inflammatory and osteogenic and osteoclast factors were examined. It was observed that treatment with SR and ALN improved the bond between the prosthesis and the surrounding bone tissue by reducing the degree of osteolysis, thus improving the quality of bone around the prosthesis. SR increased the secretion of osteocalcin, runt‑related transcription factor 2 and osteoprotegerin (OPG). It additionally decreased the expression of the receptor activator of nuclear factor‑κB ligand (RANKL) and consequently increased the protein ratio OPG/RANKL, whereas ALN exhibited the opposite effect. Furthermore, SR and ALN suppressed tumor necrosis factor‑α and interleukin‑1β production, with SR exerting a more marked effect. The present results demonstrate that SR and ALN may stimulate bone formation and inhibit bone resorption in the ovariectomized mouse model of wear particle‑mediated osteolysis, with SR demonstrating better effects compared with ALN.

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Osteoblast Response to Titanium Surfaces Coated with Strontium Ranelate–Loaded Chitosan Film

Abstract: These results indicated that SR-loaded chitosan film on a titanium surface promotes osteoblast proliferation and differentiation in a dose-dependent manner, which may represent a new approach in the treatment of a titanium implant.

Cited by 19 publications

References 0 publications

An in vivo Comparison Study Between Strontium Nanoparticles and rhBMP2

An in vivo Comparison Study Between Strontium Nanoparticles and rhBMP2

Dose-dependent Effects of Strontium Ranelate on Ovariectomy Rat Bone Marrow Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells

Effects of strontium ranelate on wear particle‑induced aseptic loosening in female ovariectomized mice

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