Regulation of osteoclasts by osteoblast lineage cells depends on titanium implant surface properties

Lotz, Ethan M.; Berger, Michael B.; Schwartz, Zvi; Boyan, Barbara D.

doi:10.1016/j.actbio.2017.12.039

Cited by 80 publications

(61 citation statements)

References 53 publications

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“…Furthermore, this is the first reported use of these transcortical implants custom‐made to fit rat femurs. Scanning electron microscopy, laser confocal microscopy, and x‐ray photoelectron spectroscopy revealed a surface morphology, average surface roughness, and surface composition similar to what has been previously reported for implants processed in the same manner …”

Section: Discussionsupporting

confidence: 81%

Ibandronate Treatment Before and After Implant Insertion Impairs Osseointegration in Aged Rats with Ovariectomy Induced Osteoporosis

et al. 2019

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Excessive decreases in bone volume (BV) and bone mineral density (BMD) can lead to osteoporosis, potentially hindering implant osseointegration. Bisphosphonates are commonly used to combat osteoporosis by slowing osteoclast‐mediated resorption; however, functional osteoclasts are integral to bone remodeling and, thus, implant osseointegration, potentially contraindicating bisphosphonate use during implantation. To optimize the use of implant technologies in patients with compromised bone structure and metabolism, we need a more complete understanding of the biological response to surface design. The goal of this study was to assess the effects of osteoporosis and bisphosphonates on osseointegration of titanium (Ti) implants with microstructured surfaces, which have been shown to support osteoblast differentiation in vitro and rapid osseointegration in vivo . Forty, 8‐month‐old, virgin, female CD Sprague Dawley rats underwent ovariectomy (OVX) or sham (SHOVX) surgery. After 5 weeks, animals were injected subcutaneously with either the bisphosphonate (BIS), Ibandronate (25 µg/kg), or phosphate‐buffered saline (PBS) every 25 days. 1 week after the initial injection, Ø2.5mm × 3.5mm microrough (SLA; grit‐blasted/acid etched) implants were placed transcortically in the distal metaphysis of each femur resulting in four groups: 1) SHOVX+PBS; 2) SHOVX+BIS; 3) OVX+PBS; and 4) OVX+BIS. After 28d, qualitative properties of the bone and implant osseointegration were assessed using micro‐computed tomography (microCT), calcified histomorphometry (Van Gieson's stain), and removal torque testing. microCT revealed decreased bone volume in OVX rats, which was slowed by bisphosphonate treatment. Reduced bone‐to‐implant contact (BIC) was evident in OVX+PBS compared to SHOVX+PBS. Although BV/TV was increased in OVX+BIS compared to OVX+PBS, bisphosphonate treatment had no effect on BIC. Removal torque testing revealed a higher maximum torque, torsional stiffness, and torsional energy in SHOVX compared to OVX with no effects due to bisphosphonate treatment. Our results show that osseointegration is decreased in osteoporotic animals. Ibandronate halts the progression of osteoporosis but does not enhance osseointegration. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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Section: Discussionsupporting

confidence: 81%

Ibandronate Treatment Before and After Implant Insertion Impairs Osseointegration in Aged Rats with Ovariectomy Induced Osteoporosis

et al. 2019

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“…Interestingly, both E2 treatment and microstructured Ti substrates are known to inhibit IL‐6 production while enhancing production of TGFβ1 and OPG (Kurebayashi et al, ; Lohmann et al, ; Schwartz et al, ). It was also shown that conditioned media from MSC cultures grown on microstructured Ti substrates for 7 days inhibit osteoclast activity and this is correlated with surface‐dependent production of osteoclast inhibitory factors (Lotz et al, ). In addition to the high production of negative regulators of osteoclast activity, cells produce high levels of osteocalcin and osteopontin (Lotz et al, , ).…”

Section: Discussionmentioning

confidence: 99%

Titanium implant surface properties enhance osseointegration in ovariectomy induced osteoporotic rats without pharmacologic intervention

Lotz

Cohen

Schwartz

et al. 2020

Clinical Oral Implants Res

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Objectives This study determined whether implant surfaces that promote osseointegration in normal rats can promote osseointegration in osteoporotic rats without pharmacologic intervention. Materials and Methods Virgin female 8‐month‐old CD Sprague Dawley rats (N = 25) were ovariectomized. At 6 weeks, microstructured/non‐nanostructured/hydrophobic, microstructured/nanostructured/hydrophobic, or microstructured/nanostructured/hydrophilic Ti implants (Ø2.5 × 3.5 mm; Institut Straumann AG, Basel, Switzerland) were placed in the distal metaphysis of each femur. At 28 days, bone quality and implant osseointegration were assessed using microCT, histomorphometrics, and removal torque values (RTVs). Calvarial osteoblasts were isolated and cultured for 7 days on Ø15 mm Ti disks processed to exhibit similar surface characteristics as the implants used for the in vivo studies. The phenotype was assessed by measuring the production of osteocalcin, osteoprotegerin, osteopontin, BMP2, VEGF, and RANKL. Results Microstructured/nanostructured/hydrophilic implants promoted increased bone‐to‐implant contact and RTVs in vivo and increased osteoblastic marker production in vitro compared to microstructured/non‐nanostructured/hydrophobic and microstructured/nanostructured/hydrophobic implants, suggesting that osseointegration occurs in osteoporotic animals, and implant surface properties improve its rate. Conclusions Although all modified implants were able to osseointegrate in rats with OVX‐induced osteoporosis without pharmacologic intervention, the degree of osseointegration was greater around microstructured/nanostructured/hydrophilic implant surfaces. These results suggest that when appropriate microstructure is present, hydrophilicity has a greater influence on Ti implant osseointegration compared to nanostructures. Moreover, modified implant surfaces can exert their control over the altered bone turnover observed in osteoporotic patients to stimulate functional osseointegration. These results provide critical insight for developing implants with improved osseointegration in patients with metabolic disorders of bone remodeling.

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“…The surface characteristics of titanium (Ti) implants affect cell adhesion, proliferation and osteoblast differentiation, which ultimately dictate the interfacial tissue formation to achieve implant fixation to the host and determine the success rate of dental implants . Modifications of Ti topography may affect osteoblast differentiation by acting on several cell mechanisms and signaling pathways, including those triggered by integrins …”

Section: Introductionmentioning

confidence: 99%

Participation of integrin β3 in osteoblast differentiation induced by titanium with nano or microtopography

Lopes

Freitas

Elias

et al. 2019

J Biomedical Materials Res

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The major role of integrins is to mediate cell adhesion but some of them are involved in the osteoblasts–titanium (Ti) interactions. In this study, we investigated the participation of integrins in osteoblast differentiation induced by Ti with nanotopography (Ti‐Nano) and with microtopography (Ti‐Micro). By using a PCR array, we observed that, compared with Ti‐Micro, Ti‐Nano upregulated the expression of five integrins in mesenchymal stem cells, including integrin β3, which increases osteoblast differentiation. Silencing integrin β3, using CRISPR‐Cas9, in MC3T3‐E1 cells significantly reduced the osteoblast differentiation induced by Ti‐Nano in contrast to the effect on T‐Micro. Concomitantly, integrin β3 silencing downregulated the expression of integrin αv, the parent chain that combines with other integrins and several components of the Wnt/β‐catenin and BMP/Smad signaling pathways, all involved in osteoblast differentiation, only in cells cultured on Ti‐Nano. Taken together, our results showed the key role of integrin β3 in the osteogenic potential of Ti‐Nano but not of Ti‐Micro. Additionally, we propose a novel mechanism to explain the higher osteoblast differentiation induced by Ti‐Nano that involves an intricate regulatory network triggered by integrin β3 upregulation, which activates the Wnt and BMP signal transductions. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1303–1313, 2019.

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Regulation of osteoclasts by osteoblast lineage cells depends on titanium implant surface properties

Cited by 80 publications

References 53 publications

Ibandronate Treatment Before and After Implant Insertion Impairs Osseointegration in Aged Rats with Ovariectomy Induced Osteoporosis

Ibandronate Treatment Before and After Implant Insertion Impairs Osseointegration in Aged Rats with Ovariectomy Induced Osteoporosis

Titanium implant surface properties enhance osseointegration in ovariectomy induced osteoporotic rats without pharmacologic intervention

Participation of integrin β3 in osteoblast differentiation induced by titanium with nano or microtopography

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