Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function

Picke, Ann-Kristin; Salbach-Hirsch, Juliane; Hintze, Vera; Rother, Sandra; Rauner, Martina; Kascholke, Christian; Möller, Stephanie; Bernhardt, Ricardo; Rammelt, Stefan; Pisabarro, M. Teresa; Ruiz-Gómez, Gloria; Schnabelrauch, Matthias; Schulz‐Siegmund, Michaela; Hacker, Michael C.; Scharnweber, Dieter; Hofbauer, Christine; Hofbauer, Lorenz C.

doi:10.1016/j.biomaterials.2016.04.013

Cited by 56 publications

(49 citation statements)

References 53 publications

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“…[22,23] The effect of sulfation of saccharides on heavy metal binding is largely unknown because it is very difficultt oo btain saccharides with defined size and sulfation pattern. [28][29][30][31] They were used to study protein glycani nteractions, for biomedical applications,a nd they are well accepted as biologically relevant GAG relatedm odels. [24][25][26] These shortcomings suggestt hat well-defined saccharides are required to study the exact effect of sulfation on metalb inding properties.…”

Section: Introductionmentioning

confidence: 99%

“…[27] Sulfated hyaluronic acids (sHA) are synthetic oligosaccharides derived from hyaluronica cid (HA) that largely resemble natives ulfated GAG such as chondroitin,d ermatan or heparan sulfate ( Figure 1A and C). [28][29][30][31] They were used to study protein glycani nteractions, for biomedical applications,a nd they are well accepted as biologically relevant GAG relatedm odels. [32][33][34][35] sHA have been successfully used to study the interactions with GAG-binding sites of many regulatory proteins and for the design of artificial extracellular matrices with tailored functions.…”

Section: Introductionmentioning

confidence: 99%

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Sulfation Patterns of Saccharides and Heavy Metal Ion Binding

Alshanski

Blaszkiewicz

Mervinetsky

et al. 2019

Chemistry A European J

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Sulfated saccharides are an essentialp art of extracellularm atrices, and they are involvedi nalarge number of interactions. Sulfated saccharide matricesi no rganismsa ccumulate heavy metal ions in addition to othere ssentialm etal ions. Accumulation of heavy metal ions alters the function of the organisms and cells, resulting in severea nd irreversible damage. The effect of the sulfation pattern of saccharides on heavym etal binding preferences is enigmatic because the accessibility to structurally definedsulfated sac-charides is limited and because standard analytical techniquescannot be used to quantify these interactions.Wedeveloped an ew strategy that combines enzymatic and chemicals ynthesis with surfacec hemistry and label-free electrochemical sensing to study the interactions between well-defined sulfated saccharides and heavy metal ions. By using these tools we showedt hat the sulfation pattern of hyaluronic acid governs their heavy metal ions binding preferences.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sulfation Patterns of Saccharides and Heavy Metal Ion Binding

Alshanski

Blaszkiewicz

Mervinetsky

et al. 2019

Chemistry A European J

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“…Low toxicity and close-to-none immunogenicity make COLL-based aECM highly compatible as graft carrier. The effect of HA on cells can be modified via controlled sulfation [28][29][30] and their precise action varies mainly related to the degree of sulfation, the location of sulfate groups within the sugar ring (sulfation pattern) and polymer length. HA is a key GAG of the skin, particularly abundant between the basal and spinous cell layers of normal human epidermis and in the cutaneous ECM.…”

Section: Introductionmentioning

confidence: 99%

Sulfated hyaluronan‐containing artificial extracellular matrices promote proliferation of keratinocytes and melanotic phenotype of melanocytes from the outer root sheath of hair follicles

Schneider

Rother

Möller

et al. 2019

J Biomedical Materials Res

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The aim of this work was to establish improved cultivation conditions for human keratinocytes (HUKORS) and melanocytes (HUMORS) from the outer root sheath (ORS) of human hair follicles for purposes of generating an epidermal graft. To this end, the cells were cultivated on artificial extracellular matrix coatings composed of collagen (COLL) and hyaluronan (HA) with varying sulfation degrees. HUKORS and HUMORS were characterized based on their morphology and proliferation, marker gene expression, protein expression and melanin content in melanocytes. Depending on the sulfation degree, the matrices provided a favorable proliferation environment for HUKORS and improved the balance between proliferation and the exertion of melanotic phenotype (gene expression and melanin content) in HUMORS. Based on the increased gene expression of microphthalmia‐associated transcription factor, as well as the downstream‐affected melanotic genes premelanosome protein and tyrosinase in HUMORS cultivated on collagen matrices with high‐sulfated HA, we assume that sulfated HA enhanced melanotic phenotype either by directly binding the CD44 receptor or by concentrating signaling mediators on site. Being a promising cultivation environment for both HUKORS and HUMORS, collagen matrices with sulfated HA have a potential of significantly improving the development of ORS‐based epidermal grafts. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1640–1653, 2019.

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“…In the same way, sulfated hyaluronan coated on biomaterials was proposed to promote osteoblast function by binding sclerostin. 5 Although the expression of Wnt inhibitors such as DKK1 and sFRP-1 was decreased in ColI-Synd2 mice, we cannot rule out that high levels of syndecan-2-conjugated heparan sulfate chains may promote sFRP-1 activity because heparin is responsible for sFRP-1 accumulation and stabilization. 38 Moreover, RSPO is a DKK1 inhibitor.…”

Section: Discussionmentioning

confidence: 86%

“…5 Thus, a key function of GAGs in fostering osteogenesis may involve modulating Wnt signaling. Indeed, in addition to sclerostin activity, that of Wnt proteins and many other Wnt modulators also depends on interactions with proteoglycans.…”

mentioning

confidence: 99%

Osteoblastic heparan sulfate glycosaminoglycans control bone remodeling by regulating Wnt signaling and the crosstalk between bone surface and marrow cells

et al. 2017

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Stimulating bone formation is an important challenge for bone anabolism in osteoporotic patients or to repair bone defects. The osteogenic properties of matrix glycosaminoglycans (GAGs) have been explored; however, the functions of GAGs at the surface of bone-forming cells are less documented. Syndecan-2 is a membrane heparan sulfate proteoglycan that is associated with osteoblastic differentiation. We used a transgenic mouse model with high syndecan-2 expression in osteoblasts to enrich the bone surface with cellular GAGs. Bone mass was increased in these transgenic mice. Syndecan-2 overexpression reduced the expression of receptor activator of NF-kB ligand (RANKL) in bone marrow cells and strongly inhibited bone resorption. Osteoblast activity was not modified in the transgenic mice, but bone formation was decreased in 4-month-old transgenic mice because of reduced osteoblast number. Increased proteoglycan expression at the bone surface resulted in decreased osteoblastic and osteoclastic precursors in bone marrow. Indeed, syndecan-2 overexpression increased apoptosis of mesenchymal precursors within the bone marrow. However, syndecan-2 specifically promoted the vasculature characterized by high expression of CD31 and Endomucin in 6-week-old transgenic mice, but this was reduced in 12-week-old transgenic mice. Finally, syndecan-2 functions as an inhibitor of Wnt-β-catenin–T-cell factor signaling pathway, activating glycogen synthase kinase 3 and then decreasing the Wnt-dependent production of Wnt ligands and R-spondin. In conclusion, our results show that GAG supply may improve osteogenesis, but also interfere with the crosstalk between the bone surface and marrow cells, altering the supporting function of osteoblasts.

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Sulfated hyaluronan improves bone regeneration of diabetic rats by binding sclerostin and enhancing osteoblast function

Cited by 56 publications

References 53 publications

Sulfation Patterns of Saccharides and Heavy Metal Ion Binding

Sulfation Patterns of Saccharides and Heavy Metal Ion Binding

Sulfated hyaluronan‐containing artificial extracellular matrices promote proliferation of keratinocytes and melanotic phenotype of melanocytes from the outer root sheath of hair follicles

Osteoblastic heparan sulfate glycosaminoglycans control bone remodeling by regulating Wnt signaling and the crosstalk between bone surface and marrow cells

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