Hyaluronan inhibits BMP‐induced osteoblast differentiation

Kaneko, Keiko; Higuchi, Chikahisa; Kunugiza, Yasuo; Yoshida, Kiyoshi; Sakai, Takashi; Yoshikawa, Hideki; Nakata, Ken

doi:10.1016/j.febslet.2014.12.031

Cited by 24 publications

(23 citation statements)

References 35 publications

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“…Moreover, it was demonstrated that sulfated HMW HA could enhance the osteogenic differentiation of human mesenchymal stem cells [44]. On the other hand, studies have also shown that cell differentiation was not affected by HMW HA [16, 45–48]. For example, Kaneko et al demonstrated that HA inhibited BMP-induced osteoblastic differentiation through the CD44 receptor in osteoblasts [45].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, studies have also shown that cell differentiation was not affected by HMW HA [16, 45–48]. For example, Kaneko et al demonstrated that HA inhibited BMP-induced osteoblastic differentiation through the CD44 receptor in osteoblasts [45]. Noteworthy, in a pure bone defect model, it was demonstrated that HA-gelatin hydrogels loaded into biphasic calcium phosphate (BCP) ceramics in rabbit femurs promoted the new bone formation and collagen mineralization [46].…”

Section: Discussionmentioning

confidence: 99%

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In vitro effects of hyaluronic acid on human periodontal ligament cells

et al. 2017

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BackgroundHyaluronic acid (HA) has been reported to have a positive effect on periodontal wound healing following nonsurgical and surgical therapy. However, to date, a few basic in vitro studies have been reported to investigating the potential of HA on human periodontal ligament (PDL) cell regeneration. Therefore, the aim of this study was to investigate the effect of HA on PDL cell compatibility, proliferation, and differentiation in vitro.MethodsEither non-cross-linked (HA_ncl) or cross-linked (HA_cl) HA was investigated. Human PDL cells were seeded in 7 conditions as follows (1) Control tissue culture plastic (TCP) (2) dilution of HA_ncl (1:100), (3) dilution of HA_ncl (1:10), 4) HA_ncl directly coated onto TCP, (5) dilution of HA_cl (1:100), 6) dilution of HA_cl (1:10) and (7) HA_cl directly coated onto TCP. Samples were then investigated for cell viability using a live/dead assay, an inflammatory reaction using real-time PCR and ELISA for MMP2, IL-1 and cell proliferation via an MTS assay. Furthermore, the osteogenic potential of PDL cells was assessed by alkaline phosphatase(ALP) activity, collagen1(COL1) and osteocalcin(OCN) immunostaining, alizarin red staining, and real-time PCR for genes encoding Runx2, COL1, ALP, and OCN.ResultsBoth HA_ncl and HA_cl showed high PDL cell viability (greater than 90%) irrespective of the culturing conditions. Furthermore, no significant difference in both mRNA and protein levels of proinflammatory cytokines, including MMP2 and IL-1 expression was observed. Both diluted HA_ncl and HA_cl significantly increased cell numbers compared to the controlled TCP samples at 3 and 5 days. HA_ncl and HA_cl in standard cell growth media significantly decreased ALP staining, COL1 immunostaining and down-regulated early osteogenic differentiation, including Runx2, COL1, and OCN mRNA levels when compared to control samples. When osteogenic differentiation medium (ODM) was added, interestingly, the expression of early osteogenic markers increased by demonstrating higher levels of COL1 and ALP expression; especially in HA 1:10 diluted condition. Late stage osteogenic markers remained inhibited.ConclusionsBoth non-cross-linked and cross-linked HA maintained high PDL cell viability, increased proliferation, and early osteogenic differentiation. However, HA was consistently associated with a significant decrease in late osteogenic differentiation of primary human PDL cells. Future in vitro and animal research is necessary to further characterize the effect of HA on periodontal regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vitro effects of hyaluronic acid on human periodontal ligament cells

et al. 2017

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“…The stimulation effect on the proliferation of periodontal ligament cells was more obvious for synthesized HA of higher concentration . Other researchers reported that the proliferation of cells cultured with the addition of high‐MW HA was not affected when compared with that of cells cultured without HA . However, other studies showed that the cell proliferation was inhibited with the presence of high‐MW HA .…”

Section: Effect Of Ha On Cell Proliferation and Differentiation In Vitromentioning

confidence: 95%

“…The effect of high‐MW HA on cell differentiation provoked controversies . On the one hand, researchers reported that cell differentiation was enhanced by high‐MW HA .…”

Section: Effect Of Ha On Cell Proliferation and Differentiation In Vitromentioning

confidence: 99%

“…Besides these receptors, some other factors have to be considered regarding the effect of MW and concentration of HA on cell proliferation and differentiation. On one hand, the delivering method of HA might play an important role . Different delivering methods of HA can lead to different length of HA–cell interaction time.…”

Section: Mechanism Of Ha On Cell Proliferation and Osteogenic Differementioning

confidence: 99%

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Effect of hyaluronic acid in bone formation and its applications in dentistry

Zhao

Wang

Qin

et al. 2016

J Biomedical Materials Res

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Hyaluronic acid (HA), the simplest glycosaminoglycan, participates in several important biological procedures, including mediation of cellular signaling, regulation of cell adhesion and proliferation, and manipulation of cell differentiation. The effect of HA on cell proliferation and differentiation depends on its molecular weight (MW) and concentration. Moreover, the properties of high viscosity, elasticity, highly negative charge, biocompatibility, biodegradability, and nonimmunogenicity make HA attractive in tissue engineering and disease treatment. This review comprises an overview of the effect of HA on cell proliferation and differentiation in vitro, the role of HA in bone regeneration in vivo, and the clinical applications of HA in dentistry, focusing on the mechanism underlining the effect of MW and concentration of HA on cell proliferation and osteogenic differentiation. It is expected that practical progress of HA both in laboratory-based experiments and clinical applications will be achieved in the next few years. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1560-1569, 2016.

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Novel In Situ Gelling Hydrogels Loaded with Recombinant Collagen Peptide Microspheres as a Slow‐Release System Induce Ectopic Bone Formation

Fahmy-Garcia

Mumcuoglu

Miguel

et al. 2018

Adv Healthcare Materials

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New solutions for large bone defect repair are needed. Here, in situ gelling slow release systems for bone induction are assessed. Collagen-I based Recombinant Peptide (RCP) microspheres (MSs) are produced and used as a carrier for bone morphogenetic protein 2 (BMP-2). The RCP-MSs are dispersed in three hydrogels: high mannuronate (SLM) alginate, high guluronate (SLG) alginate, and thermoresponsive hyaluronan derivative (HApN). HApN+RCP-MS forms a gel structure at 32 ºC or above, while SLM+RCP-MS and SLG+RCP-MS respond to shear stress displaying thixotropic behavior. Alginate formulations show sustained release of BMP-2, while there is minimal release from HApN. These formulations are injected subcutaneously in rats. SLM+RCP-MS and SLG+RCP-MS loaded with BMP-2 induce ectopic bone formation as revealed by X-ray tomography and histology, whereas HApN+RCP-MS do not. Vascularization occurs within all the formulations studied and is significantly higher in SLG+MS and HApN+RCP-MS than in SLM+RCP-MS. Inflammation (based on macrophage subset staining) decreases over time in both alginate groups, but increases in the HApN+RCP-MS condition. It is shown that a balance between inflammatory cell infiltration, BMP-2 release, and vascularization, achieved in the SLG+RCP-MS alginate condition, is optimal for the induction of de novo bone formation.

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Hyaluronan inhibits BMP‐induced osteoblast differentiation

Cited by 24 publications

References 35 publications

In vitro effects of hyaluronic acid on human periodontal ligament cells

In vitro effects of hyaluronic acid on human periodontal ligament cells

Effect of hyaluronic acid in bone formation and its applications in dentistry

Novel In Situ Gelling Hydrogels Loaded with Recombinant Collagen Peptide Microspheres as a Slow‐Release System Induce Ectopic Bone Formation

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