Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion

Simann, Meike; Schneider, Verena; Blanc, Solange Le; Dotterweich, Julia; Zehe, Viola; Krug, Melanie; Jakob, Franz; Schilling, Tatjana; Schütze, Norbert

doi:10.1016/j.bone.2015.04.039

Cited by 42 publications

(32 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Human bone marrow stromal cells (hBMSCs) were isolated from trabecular bone of femoral heads as described previously [Simann et al, ]. Patients were undergoing hip replacement surgery due to age‐related or hip dysplasia‐related attrition and were otherwise healthy.…”

Section: Methodsmentioning

confidence: 99%

“…Differentiation was induced as described earlier [Simann et al, ] in confluent hBMSC monolayers using Dulbecco's modified eagle's medium (DMEM) high glucose with L‐glutamine supplemented with 10% FBS, 100 IU/ml penicillin, and 100 μg/ml streptomycin (basal medium) according to Schilling et al []. For osteogenic differentiation, hBMSCs were incubated in osteogenic medium consisting of basal medium supplemented with 10 mM β‐glycerophosphate, 100 nM dexamethasone, and 50 μg/ml ascorbic acid phosphate for 7 or 14 days.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

et al. 2016

Self Cite

View full text Add to dashboard Cite

Controlling the adipo-osteogenic lineage decision of trabecular human bone marrow stromal cells (hBMSCs) in favor of osteogenesis represents a promising approach for osteoporosis therapy and prevention. Previously, Fibroblast Growth Factor 1 (FGF1) and its subfamily member FGF2 were scored as leading candidates to exercise control over skeletal precursor commitment and lineage decision albeit literature results are highly inconsistent. We show here that FGF1 and 2 strongly prevent the osteogenic commitment and differentiation of hBMSCs. Mineralization of extracellular matrix (ECM) and mRNA expression of osteogenic marker genes Alkaline Phosphatase (ALP), Collagen 1A1 (COL1A1), and Integrin-Binding Sialoprotein (IBSP) were significantly reduced. Furthermore, master regulators of osteogenic commitment like Runt-Related Transcription Factor 2 (RUNX2) and Bone Morphogenetic Protein 4 (BMP4) were downregulated. When administered under adipogenic culture conditions, canonical FGFs did not support osteogenic marker expression. Moreover despite the presence of osteogenic differentiation factors, FGFs even disabled the pro-osteogenic lineage decision of pre-differentiated adipocytic cells. In contrast to FGF Receptor 2 (FGFR2), FGFR1 was stably expressed throughout osteogenic and adipogenic differentiation and FGF addition. Moreover, FGFR1 and Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2) were found to be responsible for underlying signal transduction using respective inhibitors. Taken together, we present new findings indicating that canonical FGFR-ERK1/2 signaling entrapped hBMSCs in a pre-committed state and arrested further maturation of committed precursors. Our results might aid in unraveling and controlling check points relevant for ageing-associated aberrant adipogenesis with consequences for the treatment of degenerative diseases such as osteoporosis and for skeletal tissue engineering strategies. J. Cell. Biochem. 118: 263-275, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, sulfated polysaccharides such as heparin possess structural domains exhibiting affinity to various growth factors including BMPs and have been shown to form stable complexes with rhBMP-2[22–24]. Therefore, heparin is often used to immobilize rhBMP-2 onto biomaterials for a controlled protein delivery with prolonged bioactivity[25–27]. However, heparin itself suffers from natural variability in structure, difficulty in modification, non-targeting bioactivities, anticoagulant activity, and unknown physiological roles[28–33].…”

Section: Introductionmentioning

confidence: 99%

Design of hydrogels to stabilize and enhance bone morphogenetic protein activity by heparin mimetics

et al. 2018

View full text Add to dashboard Cite

Although bone morphogenetic protein-2 (BMP-2) is believed to be the most potent cytokine for bone regeneration, its clinical applications require supraphysiological BMP dosage due to its intrinsic instability and fast enzymatic degradation, leading to worrisome side effects. This study demonstrates a novel hydrogel platform that mimics a natural protector of BMPs, heparin, to sequester and stabilize BMP-2 for increased osteoinductive signaling. This study will achieve the stabilization of BMPs with prolonged bioactivity by a synthetic heparin mimic that has not been examined previously. Moreover, the heparin mimetic hydrogel surface can augment endogenous BMP activity by sequestering and localizing the cell-produced BMPs. The additional knowledge gained from this study may suggest basis for future development of material-based therapeutics for tissue engineering.

show abstract

“…Osteoporosis are induced experimentally through different methods (18)(19)(20) , one of main method to induce osteopetrosis is ovariectomy (21)(22)(23)(24)(25)(26) but it was found that rabbits constitutes a poor model for exclusively ovarian function deprivation osteoporosis. Failure in achieving significant reductions in bone mass of rabbit could be explained by presence of reflex ovulations or an ectopic production of sexual hormones (27) , so osteoporosis were induced in present study by using GCs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Effect of Platelet Rich Fibrin on Alveolar Socket Healing in Glucocorticoids-Induced Osteoporosis in Rabbits (Histological and Immuno-histomorphometric study)

2017

View full text Add to dashboard Cite

Purpose: The purpose of this study was to evaluate the effect of platelet rich fibrin on the healing of osteoporotic alveolar socket after tooth extraction in experimentally induced osteoporosis in rabbits. Materials and Methods: Thirty six adult female rabbits were used in this study. Rabbits were divided into 3 groups (group1, group2 &group 3: 12 for each group) then each group was divided into 3 subgroups (4 for each subgroups) according to the date of scarification at 7, 20, 30 days postoperatively. Group 1: (12 rabbits), alveolar socket was left empty after first molar extraction (didn't receive Platelet Rich Fibrin (PRF)). For the remaining 24 female rabbits: osteoporosis was experimentally induced by receiving 1.56 mg/kg dexamethasone (Dex) intraperitoneal injection daily for 2 months to induce osteoporosis -like condition. Group 2: (12 rabbits), osteoporotic alveolar sockets were left empty after first molar extraction (didn't receive PRF). Group 3: (12 rabbits), osteoporotic alveolar socket received PRF after first molar extraction. The specimens were collected, prepared and examined by routine haematoxylin &eosin and immunostained by Osteoprotogrin (OPG) marker. Results: at 7, 20 and 30 days, the greatest mean value was recorded in group 1, followed by group 3, with the least value recorded in group 2. Both group 1and 3 revealed a decrease in area percent of OPG throughout the study, whereas in group 2 revealed an increase. Conclusions: The study offers a clear evidence that topical application of PRF in osteoporotic alveolar socket after tooth extraction accelerates and increases the rate of bone formation and maturation than in osteoporotic alveolar socket without PRF.

show abstract

Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion

Cited by 42 publications

References 60 publications

Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

Design of hydrogels to stabilize and enhance bone morphogenetic protein activity by heparin mimetics

Evaluation of the Effect of Platelet Rich Fibrin on Alveolar Socket Healing in Glucocorticoids-Induced Osteoporosis in Rabbits (Histological and Immuno-histomorphometric study)

Contact Info

Product

Resources

About