Strontium enhances proliferation and osteogenic behavior of bone marrow stromal cells of mesenchymal and ectomesenchymal origins in vitro

Abstract

ObejectiveTo investigate the effect of increasing Strontium (Sr) concentrations on the growth and osteogenic behavior of human bone marrow stromal cells (BMSCs) from mesenchymal (i.e., fibula) and ectomesenchymal (i.e., mandible) embryonic origins.Materials and methodsFibula and mandible BMSCs were cultured in media without (Ctrl) or with Sr in four diverse concentrations: Sr1, 11.3 × 10−3 mg/L, human seric physiological level; Sr2, 13 mg/L, human seric level after strontium ranelate treatment; Sr3, 130 mg/L, and Sr4, 360 mg/L. Proliferation rate (1, 3, and 7 days), osteogenic behavior (alkaline phosphatase [ALP] activity, 7 and 14 days; expression of osteogenic genes (ALP, osteopontin, and osteocalcin at 7, 14, and 21 days), and formation of mineralized nodules (14 and 21 days) of the BMSCs were assessed. Data was compared group‐ and period‐wise using analysis of variance tests.ResultsFibula and mandible BMSCs cultured with Sr4 showed increased proliferation rate, and osteocalcin and osteopontin gene expression together with more evident formation of mineralized nodules, compared all other Sr concentrations. For both cell populations, Sr4 led to lower ALP activity, and ALP gene expression, compared with the other Sr concentrations.ConclusionBMSCs from mesenchymal (i.e., fibula) and ectomesenchymal (i.e., mandible) embryonic origins showed increased cellular proliferation and osteogenic behavior when cultured with Sr4, in vitro.

Synthesis and characterization of poly(vinyl alcohol)/chondroitin sulfate composite hydrogels containing strontium‐doped hydroxyapatite as promising biomaterials

“…This could be explained as an effect of the constituents of the control and composite hydrogels tested. CS has been shown to increase cell proliferation up to 120%, 9 whereas Sr was shown to enhance cell replication and cell functional activities, such as bone matrix synthesis and metabolic activity 56 . The absence of toxicity and increased cell number indicates that this novel composite hydrogel containing HA and HASr particles could be a promising biomedical material.…”

“…CS has been shown to increase cell proliferation up to 120%, 9 whereas Sr was shown to enhance cell replication and cell functional activities, such as bone matrix synthesis and metabolic activity. 56 The absence of toxicity and increased cell number indicates that this novel composite hydrogel containing HA and HASr particles could be a promising biomedical material. The overall manipulation of the synthesized hydrogels also showed very attractive characteristics for their clinical biomedical applications.…”

Strontium substitution of gelatin modified calcium hydrogen phosphates as porous hard tissue substitutes

“…An influence of different extracellular strontium ion concentrations in cell culture medium on osteogenic behavior of bone marrow stromal cells, periodontal ligament cells, (pre‐)osteoblasts and more has been presented in previous studies in the literature 23‐27 …”

“…The bone anabolic effect of Sr at the cellular level was shown to be dependent on the strontium ion concentrations. Bizelli‐Silveira et al, showed recently enhanced proliferation and osteogenic differentiation in vitro of periodontal ligament cells as well as bone marrow stromal cells of mesenchymal and ectomesenchymal origins when the medium was supplemented with 360 mg/L of Sr (4.1 mM, SrCl 2 ·6H 2 O), which is 30 times of human serum concentration reached after common Sr systemic supplementation used by osteoporotic women (13 mg/L) 25,26 . Verberckmoes et al, showed in an in vitro primary rat osteoblast culture, that strontium concentrations of 2 to 5 μg/ml (2.3–5.7 × 10 −3 mM, SrCl 2 ·6H 2 O) do not change mineral formation and stimulate osteoblastic differentiation, while higher concentrations (0.2–1.1 mM) did not influence osteoblast differentiation but disturbed mineral formation 23 …”

Local Release of Strontium from Sputter-Deposited Coatings at Implants Increases the Strontium-to-Calcium Ratio in Peri-implant Bone

“…, through coatings or etchings, has been shown to improve osseointegration. − ,,− As for critical size defects, strontium loading of deproteinized bone or an injectable RGD-alginate hydrogel has shown an enhanced bone regeneration as well. Also, in vitro experiments have shown increased mineralization for periodontal ligament and bone marrow stromal cells , when cultured in a medium with an addition of Sr-ions.…”