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Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Bisphosphonate coating of dental implants is a promising tool for surface modification aiming to improve the osseointegration process and clinical outcome. The biological effects of bisphosphonates are thought to be mainly associated with osteoclasts inhibition, whereas their effects on osteoblast function are unclear. A potential of bisphosphonate coated surfaces to stimulate osteoblast differentiation was investigated by several in vitro studies with contradictory results. The purpose of this systematic review and meta-analysis was to evaluate the effect of bisphosphonate coated implant surfaces on alkaline phosphatase activity in osteoblasts. METHODS:In vitro studies that assessed alkaline phosphatase activity in osteoblasts following cell culture on bisphosphonate coated titanium surfaces were searched in electronic databases PubMed/MEDLINE, Scopus and ISI Web of Science. Animal studies and clinical trials were excluded. The literature search was restricted to articles written in English and published up to August 2019. Publication bias was assessed by the construction of funnel plots. RESULTS:Eleven studies met the inclusion criteria. Meta-analysis showed that coating of titanium surfaces with bisphosphonates increases alkaline phosphatase activity in osteoblasts after 3?days (n?=?1), 7 (n?=?7), 14 (n?=?6) and 21 (n?=?3) days. (7?days beta coefficient?=?1.363, p-value?=?0.001; 14?days beta coefficient?=?1.325, p-value

SUBMITTER: Wehner C

PROVIDER: S-EPMC7183598 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis.

Wehner Christian C Lettner Stefan S Moritz Andreas A Andrukhov Oleh O Rausch-Fan Xiaohui X

BMC oral health 20200425 1

<h4>Background</h4>Bisphosphonate coating of dental implants is a promising tool for surface modification aiming to improve the osseointegration process and clinical outcome. The biological effects of bisphosphonates are thought to be mainly associated with osteoclasts inhibition, whereas their effects on osteoblast function are unclear. A potential of bisphosphonate coated surfaces to stimulate osteoblast differentiation was investigated by several in vitro studies with contradictory results. T ...[more]

PMID: 32334598

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Project description:Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/- expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.

Project description:BackgroundOsseointegration is dependent on the implant surface, surrounding bone quality, and the systemic host environment, which can differ in male and female patients. Titanium (Ti) implants with microstructured surfaces exhibit greater pullout strength when compared to smooth-surfaced implants and exhibit enhanced osteogenic cellular responses in vitro. Previous studies showed that 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] has a greater effect on rat osteoblast differentiation on microstructured Ti compared to smooth Ti surfaces and tissue culture polystyrene (TCPS). The stimulatory effect of 17β-estradiol (E2) on differentiation is observed in female osteoblasts on micro-rough Ti, but it is not known if male osteoblasts behave similarly in response to E2 and microtopography. This study assessed whether human male and female osteoblasts exhibit sex-specific differences in response to E2 and 1α,25(OH)2D3 when cultured on microstructured Ti surfaces.MethodsOsteoblasts from three male and three female human donors were cultured on Ti discs with varying surface profiles: a smooth pretreatment (PT), a coarse grit-blasted/acid-etched (SLA), and an SLA surface having undergone modification in a nitrogen environment and stored in saline to maintain hydrophilicity (modSLA). Cells cultured on these surfaces were treated with E2 or 1α,25(OH)2D3.ResultsMale and female human osteoblasts responded similarly to microstructure although there were donor-specific differences; cell number decreased, and osteocalcin (OCN), osteoprotegerin (OPG), and latent and active transforming growth factor 1 increased on SLA and modSLA compared to TCPS. Female osteoblasts had higher alkaline phosphatase activity and OCN production than male counterparts but produced less OPG. Both sexes responded similarly to 1α,25(OH)2D3. E2 treatment reduced cell number and increased osteoblast differentiation and factor production only in female cells.ConclusionsMale and female human osteoblasts respond similarly to microstructure and 1α,25(OH)2D3 but exhibit sexual dimorphism in substrate-dependent responses to E2. E2 affected female osteoblasts, suggesting that signaling is sex-specific and surface-dependent. Donor osteoblasts varied in response, demonstrating the need to test multiple donors when examining human samples. Understanding how male and female cells respond to orthopedic biomaterials will enable greater predictability post-implantation as well as therapies that are more patient-specific.

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Dataset Information

Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis.

Publications

Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis.

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