Bone-Forming Peptide-4 Induces Osteogenic Differentiation and VEGF Expression on Multipotent Bone Marrow Stromal Cells

Bone morphogenetic proteins (BMPs) have been widely used as treatment for bone repair. However, clinical trials on fracture repair have challenged the effectiveness of BMPs and suggested that delivery of multipotent bone marrow stromal cells (BMSCs) might be beneficial. During bone remodeling and bone fracture repair, multipotent BMSCs differentiate into osteoblasts or chondrocytes to stimulate bone formation and regeneration. Stem cell-based therapies provide a promising approach for bone formation. Extensive research has attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. We previously reported for the first time bone-forming peptides (BFPs) that induce osteogenesis and bone formation. BFPs are also a promising osteogenic factor for prompting bone regeneration and formation. Thus, the aim of the present study was to investigate the underlying mechanism of a new BFP-4 (FFKATEVHFRSIRST) in osteogenic differentiation and bone formation. This study reports that BFP-4 induces stronger osteogenic differentiation of BMSCs than BMP-7. BFP-4 also induces ALP activity, calcium concentration, and osteogenic factors (Runx2 and osteocalcin) in a dose dependent manner in BMSCs. Therefore, these results indicate that BFP-4 can induce osteogenic differentiation and bone formation. Thus, treatment of multipotent BMSCs with BFP-4 enhanced osteoblastic differentiation and displayed greater bone-forming ability than BMP-7 treatment. These results suggest that BFP-4-stimulated cell therapy may be an efficient and cost-effective complement to BMP-7-based clinical therapy for bone regeneration and formation.

Download Full-text

Icariin recovers the osteogenic differentiation and bone formation of bone marrow stromal cells from a rat model of estrogen deficiency-induced osteoporosis

Molecular Medicine Reports ◽

10.3892/mmr.2015.3369 ◽

2012 ◽

Vol 12 (1) ◽

pp. 382-388 ◽

Cited By ~ 18

Author(s):

ZHIQIANG LUO ◽

MINGLU LIU ◽

LIKUN SUN ◽

FEILONG RUI

Keyword(s):

Bone Marrow ◽

Bone Formation ◽

Osteogenic Differentiation ◽

Rat Model ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Estrogen Deficiency ◽

Marrow Stromal Cells

Download Full-text

PS1/γ-Secretase-Mediated Cadherin Cleavage Inducesβ-Catenin Nuclear Translocation and Osteogenic Differentiation of Human Bone Marrow Stromal Cells

Stem Cells International ◽

10.1155/2016/3865315 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Danielle C. Bonfim ◽

Rhayra B. Dias ◽

Anneliese Fortuna-Costa ◽

Leonardo Chicaybam ◽

Daiana V. Lopes ◽

...

Keyword(s):

Bone Marrow ◽

Osteogenic Differentiation ◽

Signaling Pathway ◽

Cell Fate ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Bone Repair ◽

Nuclear Translocation ◽

Marrow Stromal Cells ◽

Complex Signaling

Bone marrow stromal cells (BMSCs) are considered a promising tool for bone bioengineering. However, the mechanisms controlling osteoblastic commitment are still unclear. Osteogenic differentiation of BMSCs requires the activation ofβ-catenin signaling, classically known to be regulated by the canonical Wnt pathway. However, BMSCs treatment with canonical Wntsin vitrodoes not always result in osteogenic differentiation and evidence indicates that a more complex signaling pathway, involving cadherins, would be required to induceβ-catenin signaling in these cells. Here we showed that Wnt3a alone did not induce TCF activation in BMSCs, maintaining the cells at a proliferative state. On the other hand, we verified that, upon BMSCs osteoinduction with dexamethasone, cadherins were cleaved by the PS1/γ-secretase complex at the plasma membrane, and this event was associated with an enhancedβ-catenin translocation to the nucleus and signaling. When PS1/γ-secretase activity was inhibited, the osteogenic process was impaired. Altogether, we provide evidence that PS1/γ-secretase-mediated cadherin cleavage has as an important role in controllingβ-catenin signaling during the onset of BMSCs osteogenic differentiation, as part of a complex signaling pathway responsible for cell fate decision. A comprehensive map of these pathways might contribute to the development of strategies to improve bone repair.

Download Full-text

Periostin Mediates Oestrogen-Induced Osteogenic Differentiation of Bone Marrow Stromal Cells in Ovariectomised Rats

BioMed Research International ◽

10.1155/2020/9405909 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Chunrong Li ◽

Xin Li ◽

Xian Wang ◽

Pei Miao ◽

Jia Liu ◽

...

Keyword(s):

Bone Marrow ◽

Bone Formation ◽

Osteogenic Differentiation ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Marrow Stromal Cells ◽

Ovx Rats ◽

Novel Target

Osteoporosis is a metabolic disease that results in the progressive loss of bone mass, which, in postmenopausal women, is related to oestrogen deficiency. Periostin (POSTN) plays a key role in the early stages of bone formation. However, whether POSTN participates in oestradiol regulation of osteogenic differentiation of bone marrow stromal cells (BMSCs) from ovariectomised (OVX) rats remains unclear. In vivo, using microcomputed tomography (micro-CT), immunohistochemistry, and dynamic analysis of femurs, we found that 17β-E2 promotes bone formation and POSTN expression at the endosteal surface. In vitro, 17β-E2 upregulated POSTN expression in OVX-BMSCs. POSTN overexpression activated the Wnt/β-catenin signalling pathway and enhanced osteogenic differentiation of OVX-BMSCs. Furthermore, knockdown of Postn blocks the involvement of 17β-E2 in the osteogenic differentiation of OVX-BMSCs. Collectively, our study indicated the role of POSTN in the osteogenesis and stemness of OVX-BMSCs and proves that 17β-E2 reduces osteoporosis and promotes osteogenesis through the POSTN-Wnt/β-catenin pathway. POSTN could, therefore, be a novel target gene for anti-osteoporosis therapies.

Download Full-text

Transplanted Endothelial Cells Enhance Orthotopic Bone Regeneration

Journal of Dental Research ◽

10.1177/154405910608500710 ◽

2006 ◽

Vol 85 (7) ◽

pp. 633-637 ◽

Cited By ~ 75

Author(s):

D. Kaigler ◽

P.H. Krebsbach ◽

Z. Wang ◽

E.R. West ◽

K. Horger ◽

...

Keyword(s):

Bone Marrow ◽

Endothelial Cells ◽

Bone Formation ◽

Bone Regeneration ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Bone Matrix ◽

Marrow Stromal Cells ◽

Calvarial Defects ◽

Osseous Defect

The aim of this study was to determine if endothelial cells could enhance bone marrow stromal-cell-mediated bone regeneration in an osseous defect. Using poly-lactide-co-glycolide scaffolds as cell carriers, we transplanted bone marrow stromal cells alone or with endothelial cells into 8.5-mm calvarial defects created in nude rats. Histological analyses of blood vessel and bone formation were performed, and microcomputed tomography (μCT) was used to assess mineralized bone matrix. Though the magnitude of the angiogenic response between groups was the same, μCT analysis revealed earlier mineralization of bone in the co-transplantation condition. Ultimately, there was a significant increase (40%) in bone formation in the co-transplantation group (33 ± 2%), compared with the transplantation of bone marrow stromal cells alone (23 ± 3%). Analysis of these data demonstrates that, in an orthotopic site, transplanted endothelial cells can influence the bone-regenerative capacity of bone marrow stromal cells.

Download Full-text

Design of hydroxyapatite bioceramics with micro-/nano-topographies to regulate the osteogenic activities of bone morphogenetic protein-2 and bone marrow stromal cells

Nanoscale ◽

10.1039/c9nr10561a ◽

2020 ◽

Vol 12 (13) ◽

pp. 7284-7300 ◽

Cited By ~ 5

Author(s):

Xiangfeng Li ◽

Minjun Liu ◽

Fuying Chen ◽

Yuyi Wang ◽

Menglu Wang ◽

...

Keyword(s):

Bone Marrow ◽

Bone Regeneration ◽

Bone Morphogenetic Protein ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Marrow Stromal Cells ◽

Bone Morphogenetic Protein 2 ◽

Natural Bone ◽

Morphogenetic Protein ◽

Bone Apatite

Biomimicking the nanostructure of natural bone apatite to enhance the bioactivity of hydroxyapatite (HA) biomaterials is an eternal topic in the bone regeneration field.

Download Full-text

Accelerated bone repair with the use of a synthetic BMP-2-derived peptide and bone-marrow stromal cells

Journal of Biomedical Materials Research ◽

10.1002/jbm.a.30208 ◽

2004 ◽

Vol 72A (1) ◽

pp. 77-82 ◽

Cited By ~ 78

Author(s):

Atsuhiro Saito ◽

Yoshihisa Suzuki ◽

Shin-Ichi Ogata ◽

Chikara Ohtsuki ◽

Masao Tanihara

Keyword(s):

Bone Marrow ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Bone Repair ◽

Marrow Stromal Cells

Download Full-text

Activation of 4-1BB signaling in bone marrow stromal cells triggers bone loss via the p-38 MAPK-DKK1 axis in aged mice

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00605-y ◽

2021 ◽

Author(s):

Daqian Wan ◽

Songtao Ai ◽

Huoniu Ouyang ◽

Liming Cheng

Keyword(s):

Bone Marrow ◽

Bone Loss ◽

Osteogenic Differentiation ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Bone Marrow Microenvironment ◽

Marrow Stromal Cells ◽

Senile Osteoporosis ◽

Aged Mice ◽

Old Mice

AbstractSenile osteoporosis can cause bone fragility and increased fracture risks and has been one of the most prevalent and severe diseases affecting the elderly population. Bone formation depends on the proper osteogenic differentiation of bone marrow stromal cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types in the bone marrow. With aging, bone marrow provides signals that repress osteogenesis. Finding the signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the abnormal changes in BMSCs with aging are key to elucidating the mechanisms of senile osteoporosis. In a pilot experiment, we found that 4-1BBL and 4-1BB were more abundant in bone marrow from aged (18-month-old) mice than young (6-month-old) mice. Meanwhile, significant bone loss was observed in aged mice compared with young mice. However, very little data have been generated regarding whether high-level 4-1BB/4-1BBL in bone marrow was associated with bone loss in aged mice. In the current study, we found upregulation of 4-1BB in the BMSCs of aged mice, which resulted in the attenuation of the osteogenic differentiation potential of BMSCs from aged mice via the p38 MAPK-Dkk1 pathway. More importantly, bone loss of aged mice could be rescued through the blockade of 4-1BB signaling in vivo. Our study will benefit not only our understanding of the pathogenesis of age-related trabecular bone loss but also the search for new targets to treat senile osteoporosis.

Download Full-text