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 12/2011

01-12-2011 | Original Paper

Synergistic effect of recombinant human bone morphogenic protein-7 and osteogenic differentiation medium on human bone-marrow-derived mesenchymal stem cells in vitro

Authors: Lianteng Zhi, Chao Chen, Xiaoli Pang, Hasan Uludag, Hongxing Jiang

Published in: International Orthopaedics | Issue 12/2011

Login to get access

Abstract

Purpose

The purpose of this study was to investigate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) with or without osteogenic differentiation medium (ODM) on osteogenic differentiation of primary human bone-marrow-derived mesenchymal stem cells (hBMSCs) in vitro.

Method

The hBMSCs were isolated from medullary reaming tissue. At 80% confluence, hBMSCs were treated with different concentrations of rhBMP-7 with and without ODM. Alkaline phosphatase (ALP) activity, calcium deposition and messenger RNA (mRNA) expression of osteocalcin (OC) and osteopontin (OPN) were examined.

Results

ALP activity and calcium deposits in hBMSC culture were significantly increased by rhBMP-7 at 0.1 μg/ml (0.23 ± 0.07 IU and 28.9 ± 4.2 mg/dl) and 1.0 μg/ml (0.32 ± 0.03 IU and 38.7 ± 3.0 mg/dl), respectively, in the presence of ODM, showing a clearly dose-dependent osteoblastic differentiation. However, the same dose of 0.1 μg/ml rhBMP-7 without ODM and ODM alone induced low level of ALP and calcium deposits, indicating a synergistic effect of rhBMP-7 and ODM on committed osteogenic differentiation. Quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed up-regulated OC and OPN mRNA levels, corroborating the synergistic effect of rhBMP-7 and ODM.

Conclusion

Our study showed that rhBMP-7 with ODM created a synergistic effect on up-regulation of osteogenic genes as well as osteogenic differentiation of primary hBMSCs in vitro. In the presence of ODM, the lowest concentration of rhBMP-7 needed to induce significant osteogenic differentiation of hBMSCs was 0.1 μg/ml.
Literature
1.
Pecina M, Giltaij LR, Vukicevic S (2001) Orthopaedic applications of osteogenic protein-1 (BMP-7). Int Orthop 25:203–208PubMedCrossRef
2.
Bilic R, Simic P, Jelic M, Stern-Padovan R, Dodig D, van Meerdervoort HP, Martinovic S, Ivankovic D, Pecina M, Vukicevic S (2006) Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis. Int Orthop 30:128–134PubMedCrossRef
3.
Mihelic R, Pecina M, Jelic M, Zoricic S, Kusec V, Simic P, Bobinac D, Lah B, Legovic D, Vukicevic S (2004) Bone morphogenetic protein-7 (osteogenic protein-1) promotes tendon graft integration in anterior cruciate ligament reconstruction in sheep. Am J Sports Med 32:1619–1625PubMedCrossRef
4.
Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF, Zych GA, Calhoun JH, LaForte AJ, Yin S (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 83-A(Suppl 1):S151–S158PubMed
5.
Geesink RG, Hoefnagels NH, Bulstra SK (1999) Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. J Bone Joint Surg Br 81:710–718PubMedCrossRef
6.
Makino T, Hak DJ, Hazelwood SJ, Curtiss S, Reddi AH (2005) Prevention of atrophic nonunion development by recombinant human bone morphogenetic protein-7. J Orthop Res 23:632–638PubMedCrossRef
7.
Issack PS, DiCesare PE (2003) Recent advances toward the clinical application of bone morphogenetic proteins in bone and cartilage repair. Am J Orthop 32:429–436PubMed
8.
White AP, Vaccaro AR, Hall JA, Whang PG, Friel BC, McKee MD (2007) Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusion. Int Orthop 31:735–741PubMedCrossRef
9.
Mehrara BJ, Saadeh PB, Steinbrech DS, Dudziak M, Spector JA, Greenwald JA, Gittes GK, Longaker MT (1999) Adenovirus-mediated gene therapy of osteoblasts in vitro and in vivo. J Bone Miner Res 14:1290–1301PubMedCrossRef
10.
Diefenderfer DL, Osyczka AM, Garino JP, Leboy PS (2003) Regulation of BMP-induced transcription in cultured human bone marrow stromal cells. J Bone Joint Surg Am 85-A(Suppl 3):19–28PubMed
11.
Paul S, Lee JC, Yeh LC (2009) A comparative study on BMP-induced osteoclastogenesis and osteoblastogenesis in primary cultures of adult rat bone marrow cells. Growth Factors 27:121–131PubMedCrossRef
12.
Yeh LC, Tsai AD, Lee JC (2002) Osteogenic protein-1 (OP-1, BMP-7) induces osteoblastic cell differentiation of the pluripotent mesenchymal cell line C2C12. J Cell Biochem 87:292–304PubMedCrossRef
13.
Laflamme C, Rouabhia M (2008) Effect of BMP-2 and BMP-7 homodimers and a mixture of BMP-2/BMP-7 homodimers on osteoblast adhesion and growth following culture on a collagen scaffold. Biomed Mater 3:15008CrossRef
14.
Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP (1997) Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64:295–312PubMedCrossRef
15.
Jiang H, Secretan C, Gao T, Bagnall K, Korbutt G, Lakey J, Jomha NM (2006) The development of osteoblasts from stem cells to supplement fusion of the spine during surgery for AIS. Stud Health Technol Inform 123:467–472PubMed
16.
Orimo H, Shimada T (2008) The role of tissue-nonspecific alkaline phosphatase in the phosphate-induced activation of alkaline phosphatase and mineralization in SaOS-2 human osteoblast-like cells. Mol Cell Biochem 315:51–60PubMedCrossRef
17.
Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17:331–340PubMedCrossRef
18.
Friedenstein AJ, Chailakhyan RK, Gerasimov UV (1987) Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 20:263–272PubMed
19.
Owen M, Friedenstein AJ (1988) Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 136:42–60PubMed
20.
Leboy PS, Beresford JN, Devlin C, Owen ME (1991) Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures. J Cell Physiol 146:370–380PubMedCrossRef
21.
Locklin RM, Williamson MC, Beresford JN, Triffitt JT, Owen ME (1995) In vitro effects of growth factors and dexamethasone on rat marrow stromal cells. Clin Orthop Relat Res 313:27–35PubMed
22.
Jäger M, Fischer J, Dohrn W, Li X, Ayers DC, Czibere A, Prall WC, Lensing-Hohn S, Krauspe R (2008) Dexamethasone modulates BMP-2 effects on mesenchymal stem cells in vitro. J Orthop Res 26:1440–1448PubMedCrossRef
23.
Xu LL, Liu HC, Wang DS ELL, Xu L, Jin ZL, Duan YZ (2009) Effects of BMP-2 and dexamethasone on osteogenic differentiation of rat dental follicle progenitor cells seeded on three-dimensional beta-TCP. Biomed Mater 4:065010PubMedCrossRef
24.
Mikami Y, Asano M, Honda MJ, Takagi M (2010) Bone morphogenetic protein 2 and dexamethasone synergistically increase alkaline phosphatase levels through JAK/STAT signaling in C3H10T1/2 cells. J Cell Physiol 223:123–133PubMed
25.
Mikami Y, Lee M, Irie S, Honda MJ (2011) Dexamethasone modulates osteogenesis and adipogenesis with regulation of osterix expression in rat calvaria-derived cells. J Cell Physiol 226:739–748PubMedCrossRef
26.
Hu J, Smith LA, Feng K, Liu X, Sun H, Ma PX (2010) Response of human embryonic stem cell-derived mesenchymal stem cells to osteogenic factors and architectures of materials during in vitro osteogenesis. Tissue Eng A 16:3507–3514CrossRef
27.
Yamaguchi A, Komori T, Suda T (2000) Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev 21:393–411PubMedCrossRef
28.
Morinobu M, Ishijima M, Rittling SR, Tsuji K, Yamamoto H, Nifuji A, Denhardt DT, Noda M (2003) Osteopontin expression in osteoblasts and osteocytes during bone formation under mechanical stress in the calvarial suture in vivo. J Bone Miner Res 18:1706–1715PubMedCrossRef
Metadata
Title
Synergistic effect of recombinant human bone morphogenic protein-7 and osteogenic differentiation medium on human bone-marrow-derived mesenchymal stem cells in vitro
Authors
Lianteng Zhi
Chao Chen
Xiaoli Pang
Hasan Uludag
Hongxing Jiang
Publication date
01-12-2011
Publisher
Springer-Verlag
Published in
International Orthopaedics / Issue 12/2011
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-011-1247-1

Other articles of this Issue 12/2011

International Orthopaedics 12/2011 Go to the issue

Original Paper

Scorpio single radius total knee arthroplasty. A minimal five-year follow-up multicentric study

Original Paper

Hemi-Castaing ligamentoplasty for the treatment of chronic lateral ankle instability: a retrospective assessment of outcome

Original Paper

Effects of pulsed electromagnetic fields on cartilage apoptosis signalling pathways in ovariectomised rats

Original Paper

Prospective randomised study comparing screw versus helical blade in the treatment of low-energy trochanteric fractures

Letter to the Editor

Reply to the comments of Li et al. to the article: Posterior wall reconstruction using iliac crest strut graft in severely comminuted posterior acetabular wall fracture

Original Paper

International survey of primary and revision total knee replacement