Biglycan in the Skeleton

Kram, Vardit; Shainer, Reut; Jani, Priyam; Meester, Josephina; Loeys, Bart; Young, Marian F.

doi:10.1369/0022155420937371

Cited by 37 publications

(28 citation statements)

References 253 publications

(214 reference statements)

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“…The expression of OSX, despite following a similar trend to RUNX-2, was not found to be significantly increased due to a big data spread. On day 10 of differentiation, the mid-term osteogenic markers BGN and DCN, which are associated with matrix mineralization in vitro 72 , 73 , also showed a significantly increased expression in cells cultured on O-NCD + BMP-7 in comparison with other materials. These results correspond with the matrix mineralization results on day 10 assessed by Alizarin Red S staining.…”

Section: Resultsmentioning

confidence: 96%

Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo

Nemcakova

Litvinec

Mandys

et al. 2022

Sci Rep

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The present study investigates the effect of an oxidized nanocrystalline diamond (O-NCD) coating functionalized with bone morphogenetic protein 7 (BMP-7) on human osteoblast maturation and extracellular matrix mineralization in vitro and on new bone formation in vivo. The chemical structure and the morphology of the NCD coating and the adhesion, thickness and morphology of the superimposed BMP-7 layer have also been assessed. The material analysis proved synthesis of a conformal diamond coating with a fine nanostructured morphology on the Ti6Al4V samples. The homogeneous nanostructured layer of BMP-7 on the NCD coating created by a physisorption method was confirmed by AFM. The osteogenic maturation of hFOB 1.19 cells in vitro was only slightly enhanced by the O-NCD coating alone without any increase in the mineralization of the matrix. Functionalization of the coating with BMP-7 resulted in more pronounced cell osteogenic maturation and increased extracellular matrix mineralization. Similar results were obtained in vivo from micro-CT and histological analyses of rabbit distal femurs with screws implanted for 4 or 12 weeks. While the O-NCD-coated implants alone promoted greater thickness of newly-formed bone in direct contact with the implant surface than the bare material, a further increase was induced by BMP-7. It can be therefore concluded that O-NCD coating functionalized with BMP-7 is a promising surface modification of metallic bone implants in order to improve their osseointegration.

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Section: Resultsmentioning

confidence: 96%

Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo

Nemcakova

Litvinec

Mandys

et al. 2022

Sci Rep

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“…Indeed, by regulating signal transduction mechanisms, these molecules affect basal cellular functions, such as proliferation, migration, and differentiation [ 8 , 11 ]. An important example is that SLRP interaction with growth factors, and their respective tyrosine kinase receptors, regulates key downstream intracellular signaling pathways [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Biglycan Interacts with Type I Insulin-like Receptor (IGF-IR) Signaling Pathway to Regulate Osteosarcoma Cell Growth and Response to Chemotherapy

Giatagana

Berdiaki

Gaardløs

et al. 2022

Cancers

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Osteosarcoma (OS) is a mesenchymally derived, aggressive bone cancer. OS cells produce an aberrant nonmineralized or partly mineralized extracellular matrix (ECM) whose components participate in signaling pathways connected to specific pathogenic phenotypes of this bone cancer. The expression of biglycan (BGN), a secreted small leucine-rich proteoglycan (SLRP), is correlated to aggressive OS phenotype and resistance to chemotherapy. A constitutive signaling of IGF-IR signaling input in sarcoma progression has been established. Here, we show that biglycan activates the IGF-IR signaling pathway to promote MG63 biglycan-secreting OS cell growth by forming a complex with the receptor. Computational models of IGF-IR and biglycan docking suggest that biglycan binds IGF-IR dimer via its concave surface. Our binding free energy calculations indicate the formation of a stable complex. Biglycan binding results in prolonged IGF-IR activation leading to protracted IGF-IR-dependent cell growth response of the poorly-differentiated MG63 cells. Moreover, biglycan facilitates the internalization (p ≤ 0.01, p ≤ 0.001) and sumoylation-enhanced nuclear translocation of IGF-IR (p ≤ 0.05) and its DNA binding in MG63 cells (p ≤ 0.001). The tyrosine kinase activity of the receptor mediates this mechanism. Furthermore, biglycan downregulates the expression of the tumor-suppressor gene, PTEN (p ≤ 0.01), and increases the expression of endothelial–mesenchymal transition (EMT) and aggressiveness markers vimentin (p ≤ 0.01) and fibronectin (p ≤ 0.01) in MG63 cells. Interestingly, this mechanism is not valid in moderately and well-differentiated, biglycan non-expressing U-2OS and Saos-2 OS cells. Furthermore, biglycan exhibits protective effects against the chemotherapeutic drug, doxorubicin, in MG63 OS cells (p ≤ 0.01). In conclusion, these data indicate a potential direct and adjunct therapeutical role of biglycan in osteosarcoma.

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“…Apart from the TGF-β/BMP signaling, Bgn is shown to trigger the Wnt pathway by binding to the canonical Wnt ligand Wnt3a as well as the Wnt receptor low density lipoprotein receptor-related protein 6 (LRP6). Both glycosylated and non-glycosylated forms of Bgn are shown to activate this signaling pathway [36] , [37] . Bgn also plays a crucial role in ERK phosphorylation and signal transduction through the transcription factor Runx2 [38] .…”

Section: Introductionmentioning

confidence: 99%

“…Although Dcn deficiency also introduces changes in collagen fibril size and shape in bone, no major changes in bone mass or architecture are observed in these mice [31] . Due to the structural similarity of Bgn and Dcn, a compensatory mechanism is likely triggered when either is ablated, leading to an increased expression of the other, which could partially be explained by clustering of SLRP family members genes on their respective chromosomes [33] , [37] , [43] . Consistently, Dcn / Bgn double KO mice exhibit more severe skin and bone phenotypes than either single Bgn or Dcn KO models [31] .…”

Section: Introductionmentioning

confidence: 99%

“…Consistently, the GAG chains of fibromodulin are shortened with aging until the non-glycanated form becomes the predominant one [94] . These age-related changes of PGs can be a result of an increased rate of degradation of their glycanated precursors, or changes in growth factor/cytokine synthesis with aging [37] , [95] . In addition to PGs, the ratio of bound water and free water in bone matrix also changes during aging.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Small leucine-rich proteoglycans in physiological and biomechanical function of bone

Hua

Jiang

2021

Matrix Biology Plus

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Highlights Proteoglycans (PGs) and glycosaminoglycans (GAGs) play vital roles in key signaling pathways to regulate bone homeostasis. The highly negatively charged GAGs are crucial in retaining bound water and modulating mechanical properties of bone. Age-related changes of PGs, GAGs, and bound water contribute to deterioration of bone quality during aging.

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Biglycan in the Skeleton

Cited by 37 publications

References 253 publications

Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo

Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo

Biglycan Interacts with Type I Insulin-like Receptor (IGF-IR) Signaling Pathway to Regulate Osteosarcoma Cell Growth and Response to Chemotherapy

Small leucine-rich proteoglycans in physiological and biomechanical function of bone

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