Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
International Orthopaedics
Published in: International Orthopaedics 4/2018

01-04-2018 | Original Paper

Cyclic mechanical stretch enhances BMP9-induced osteogenic differentiation of mesenchymal stem cells

Authors: Yang Song, Yinhong Tang, Jinlin Song, Mingxing Lei, Panpan Liang, Tiwei Fu, Xudong Su, Pengfei Zhou, Li Yang, Enyi Huang

Published in: International Orthopaedics | Issue 4/2018

Login to get access

Abstract

Purpose

The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs.

Methods

Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours. Immunostaining and confocal microscope were used to detect cytoskeleton organization. Cell cycle progression was checked by flow cytometry. Alkaline phosphatase activity was measured with a Chemiluminescence Assay Kit and was quantified with a histochemical staining assay. Matrix mineralization was examined by Alizarin Red S Staining.

Results

Mechanical stretch induces cytoskeleton reorganization and inhibits cell proliferation by preventing cells entry into S phase of the cell cycle. Although mechanical stretch alone does not induce the osteogenic differentiation of C3H10T1/2 MSCs, co-stimulation with mechanical stretch and BMP9 enhances alkaline phosphatase activity. The expression of key lineage-specific regulators (e.g., osteocalcin (OCN), SRY-related HMG-box 9, and runt-related transcription factor 2) is also increased after the co-stimulation, compared to the mechanical stretch stimulation along. Furthermore, mechanical stretch augments the BMP9-mediated bone matrix mineralization of C3H10T1/2 MSCs.

Conclusions

Our results suggest that mechanical stretch enhances BMP9-induced osteoblastic lineage specification in C3H10T1/2 MSCs.
Literature
1.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147CrossRefPubMed
2.
Lee JH, Park HK, Kim KS (2015) Intrinsic and extrinsic mechanical properties related to the differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 473(3):752–757CrossRefPubMed
3.
Beederman M, Lamplot JD, Nan G, Wang J, Liu X, Yin L, Li R, Wei S, Zhang H, Kim SH (2013) BMP signaling in mesenchymal stem cell differentiation and bone formation. J Biomed Sci Eng 6(8A):32–52CrossRefPubMedPubMedCentral
4.
Varga AC, Wrana JL (2005) The disparate role of BMP in stem cell biology. Oncogene 24(37):5713–5721CrossRefPubMed
5.
Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P (2003) Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg (Am Vol) 85-A(8):79–80
6.
Kang Q, Song WX, Luo Q, Tang N, Luo J, Luo X, Chen J, Bi Y, He BC, Park JK (2009) A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells. Stem Cells Dev 18(4):545–559CrossRefPubMed
7.
Sun L, Qu L, Zhu R, Li H, Xue Y, Liu X, Fan J, Fan H (2016) Effects of mechanical stretch on cell proliferation and matrix formation of mesenchymal stem cell and anterior cruciate ligament fibroblast. Stem Cells Int 2016:1):1–1)10
8.
Luo J, Deng ZL, Luo X, Tang N, Song WX, Chen J, Sharff KA, Luu HH, Haydon RC, Kinzler KW (2007) A protocol for rapid generation of recombinant adenoviruses using the AdEasy system. Nat Protoc 2(5):1236–1247CrossRefPubMed
9.
Huang E, Zhu G, Jiang W, Yang K, Gao Y, Luo Q, Gao JL, Kim SH, Liu X, Li M (2012) Growth hormone synergizes with BMP9 in osteogenic differentiation by activating the JAK/STAT/IGF1 pathway in murine multilineage cells. J Bone Miner Res 27(7):1566–1575CrossRefPubMed
10.
Zhang W, Deng ZL, Chen L, Zuo GW, Luo Q, Shi Q, Zhang BQ, Wagner ER, Rastegar F, Kim SH (2010) Retinoic acids potentiate BMP9-induced osteogenic differentiation of mesenchymal progenitor cells. PLoS One 5(7):58–72
11.
Chen L, Jiang W, Huang J, He BC, Zuo GW, Zhang W, Luo Q, Shi Q, Zhang BQ, Wagner ER (2010) Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res 25(11):2447–2459CrossRefPubMedPubMedCentral
12.
Hu N, Jiang D, Huang E, Liu X, Li R, Liang X, Kim SH, Chen X, Gao JL, Zhang H (2013) BMP9-regulated angiogenic signaling plays an important role in the osteogenic differentiation of mesenchymal progenitor cells. J Cell Sci 126(2):532–541CrossRefPubMedPubMedCentral
13.
Iura A, Mcnerny EG, Zhang Y, Kamiya N, Tantillo M, Lynch M, Kohn DH, Mishina Y (2015) Mechanical loading synergistically increases trabecular bone volume and improves mechanical properties in the mouse when BMP signaling is specifically ablated in osteoblasts. PLoS One 10(10):e0141345CrossRefPubMedPubMedCentral
14.
Xiao E, Yang HQ, Gan YH, Duan DH, He LH, Guo YB, Wang SQ, Zhang Y (2014) TRPM7 senses mechanical stimulation inducing Osteogenesis in human bone marrow Mesenchymal stem cells. Stem Cells 33(2):615–621CrossRef
15.
16.
Ehrlicher AJ, Nakamura F, Hartwig JH, Weitz DA, Stossel TP (2011) Mechanical strain in actin networks regulates FilGAP and integrin binding to filamin a. Nature 478(7368):260–263CrossRefPubMedPubMedCentral
17.
Konstantinidis G, Moustakas A, Stournaras C (2011) Regulation of myosin light chain function by BMP signaling controls actin cytoskeleton remodeling. Cell Physiol Biochem 28(5):1031–1044CrossRefPubMed
18.
Das RK, Gocheva V, Hammink R, Zouani OF, Rowan A (2015) Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels. Nat Mater 15(3):318–325CrossRefPubMed
19.
Wu Y, Zhang P, Dai Q, Yang X, Fu R, Jiang L, Fang B (2013) Effect of mechanical stretch on the proliferation and differentiation of BMSCs from ovariectomized rats. Mol Cell Biochem 382(1):273–282CrossRefPubMed
20.
Song G, Yang J, Shen X, Luo Q, Shi Y, Qin J (2007) Mechanical stretch promotes proliferation of rat bone marrow mesenchymal stem cells. Colloids Surf B Biointerfaces 58(2):271–277CrossRefPubMed
21.
Sun L, Ling Q, Rui Z, Li H, Xue Y, Liu X, Fan J, Fan H (2016) Effects of mechanical stretch on cell proliferation and matrix formation of mesenchymal stem cell and anterior cruciate ligament fibroblast. Stem Cells Int 2016:1):1–1)10
22.
Nakamura A, Dohi Y, Akahane M, Ohgushi H, Nakajima H, Funaoka H, Takakura Y (2009) Osteocalcin secretion as an early marker of in vitro osteogenic differentiation of rat mesenchymal stem cells. Tissue Eng Part C Methods 15(2):169–180CrossRefPubMed
23.
Shenaq DS, Teven CM, Seitz IA, Rastegar F, Greives MR, He TC, Reid RR (2015) Characterization of reversibly immortalized calvarial mesenchymal progenitor cells. J Craniofac Surg 26(4):1207–1213CrossRefPubMedPubMedCentral
24.
Gu K, Zhang L, Jin T, Rutherford RB (2004) Identification of potential modifiers of Runx2/Cbfa1 activity in C2C12 cells in response to bone morphogenetic protein-7. Cells Tissues Organs 176(1–3):28CrossRefPubMed
25.
Kupcsik L, Stoddart MJ, Li Z, Benneker LM, Alini M (2010) Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering. Tissue Eng A 16(6):1845–1855CrossRef
26.
Beederman M, Lamplot JD, Nan G, Wang J, Liu X, Yin L, Li R, Shui W, Zhang H, Kim SH (2013) BMP signaling in mesenchymal stem cell differentiation and bone formation. J Biomed Sci Eng 6(8A):32–52CrossRefPubMedPubMedCentral
27.
Kanazawa T, Furumatsu T, Hachioji M, Oohashi T, Ninomiya Y, Ozaki T (2012) Mechanical stretch enhances COL2A1 expression on chromatin by inducing SOX9 nuclear translocalization in inner meniscus cells. J Orthop Res 30(3):468–474CrossRefPubMed
Metadata
Title
Cyclic mechanical stretch enhances BMP9-induced osteogenic differentiation of mesenchymal stem cells
Authors
Yang Song
Yinhong Tang
Jinlin Song
Mingxing Lei
Panpan Liang
Tiwei Fu
Xudong Su
Pengfei Zhou
Li Yang
Enyi Huang
Publication date
01-04-2018
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 4/2018
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-018-3796-z

Other articles of this Issue 4/2018

International Orthopaedics 4/2018 Go to the issue

Original Paper

Natural history of the ossification of cervical posterior longitudinal ligament: a three dimensional analysis

Original Paper

Humeral head inferior subluxation in proximal humerus fractures

Letter to the Editor

In regard to the letter by Li and Yang on the article “Which immobilization is better for distal radius fracture? A prospective randomized trial”

Original Paper

Peri-operative antibiotic treatment of bacteriuria reduces early deep surgical site infections in geriatric patients with proximal femur fracture

Correction

Correction to: Ambroise Paré (1510–1590): on the diagnosis and treatment of shoulder dislocations

Original Paper

Factors influencing recurrence and progression of Dupuytren’s disease treated by Collagenase Clostridium histolitycum