title: Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair.
abstract: The extracellular matrix-associated bone morphogenetic proteins (BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell (MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted cell-type lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.
authors.affiliation: Sonia Scarfì, Department of Earth, Environment and Life Sciences, University of Genova, 16132 Genova, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Scarfì
keywords: Bone morphogenetic protein; Bone repair; Cartilage; Mesenchymal stem cells
references.citation: J Bone Miner Res. 1999 Dec;14 (12 ):2015-26
references.pmid: 10620060
references.citation: Development. 1997 Jun;124(12):2325-34
references.pmid: 9199359
references.citation: J Bone Joint Surg Am. 1997 Dec;79(12 ):1778-90
references.pmid: 9409791
references.citation: ANZ J Surg. 2007 Aug;77(8):626-31
references.pmid: 17635273
references.citation: Clin Orthop Relat Res. 2009 Dec;467(12 ):3257-62
references.pmid: 19693635
references.citation: Front Biosci (Landmark Ed). 2013 Jun 01;18:1407-34
references.pmid: 23747893
references.citation: Mol Ther. 2005 Aug;12(2):219-28
references.pmid: 16043093
references.citation: Bone. 2010 Jul;47(1):117-26
references.pmid: 20362702
references.citation: J Chin Med Assoc. 2008 Feb;71(2):66-73
references.pmid: 18290250
references.citation: Endocrinology. 1992 Mar;130(3):1318-24
references.pmid: 1311236
references.citation: Science. 1965 Nov 12;150(3698):893-9
references.pmid: 5319761
references.citation: Dev Biol. 2000 Mar 15;219(2):237-49
references.pmid: 10694419
references.citation: Int Orthop. 2011 Sep;35(9):1271-80
references.pmid: 21698428
references.citation: J Cell Biochem. 2010 Feb 1;109(2):406-16
references.pmid: 19950204
references.citation: World J Stem Cells. 2014 Apr 26;6(2):153-62
references.pmid: 24772242
references.citation: Development. 1997 Mar;124(6):1109-17
references.pmid: 9102298
references.citation: Protein Sci. 2014 Aug;23(8):999-1012
references.pmid: 24810382
references.citation: Science. 1993 May 14;260(5110):920-6
references.pmid: 8493529
references.citation: Laryngoscope. 2010 May;120(5):895-901
references.pmid: 20422682
references.citation: Discov Med. 2012 Jan;13(68):57-63
references.pmid: 22284784
references.citation: J Bone Joint Surg Br. 1999 Jul;81(4):710-8
references.pmid: 10463751
references.citation: J Orthop Res. 2003 Jan;21(1):44-53
references.pmid: 12507579
references.citation: Genes Dis. 2014 Sep;1(1):87-105
references.pmid: 25401122
references.citation: J Orthop Surg Res. 2015 May 14;10:66
references.pmid: 25968127
references.citation: Haematol Blood Transfus. 1980;25:19-29
references.pmid: 7021339
references.citation: Tissue Eng. 2005 Jul-Aug;11(7-8):1159-67
references.pmid: 16144452
references.citation: J Biol Chem. 1994 Nov 11;269(45):28227-34
references.pmid: 7961761
references.citation: Chin Med J (Engl). 2015 Apr 20;128(8):1121-7
references.pmid: 25881610
references.citation: J Biochem. 2012 Mar;151(3):247-54
references.pmid: 22253449
references.citation: J Cell Biochem. 2006 Jun 1;98(3):538-54
references.pmid: 16317727
references.citation: Mech Dev. 1996 Jul;57(2):145-57
references.pmid: 8843392
references.citation: Exp Cell Res. 2008 Aug 1;314(13):2400-10
references.pmid: 18565511
references.citation: Cytokine Growth Factor Rev. 2012 Feb-Apr;23(1-2):61-7
references.pmid: 22421241
references.citation: J Orthop Res. 1999 Jan;17(1):43-50
references.pmid: 10073646
references.citation: J Bone Miner Res. 2002 Mar;17(3):513-20
references.pmid: 11874242
references.citation: Clin Orthop Relat Res. 1999 Oct;(367 Suppl):S147-55
references.pmid: 10546643
references.citation: Mol Ther. 2001 Apr;3(4):449-61
references.pmid: 11319905
references.citation: Instr Course Lect. 1998;47:487-504
references.pmid: 9571450
references.citation: J Cell Physiol. 2009 Feb;218(2):237-45
references.pmid: 18792913
references.citation: J Cell Physiol. 2001 Dec;189(3):275-84
references.pmid: 11748585
references.citation: Biorheology. 2000;37(1-2):163-4
references.pmid: 10912188
references.citation: J Bone Joint Surg Am. 2003;85-A Suppl 2:111-6
references.pmid: 12721353
references.citation: J Cell Sci. 2005 Aug 15;118(Pt 16):3573-84
references.pmid: 16105881
references.citation: Arthritis Rheum. 2006 Apr;54(4):1222-32
references.pmid: 16572454
references.citation: Arthritis Rheum. 2007 Jun;56(6):1869-79
references.pmid: 17530715
references.citation: Am J Sports Med. 2011 Jan;39(1):180-7
references.pmid: 20956264
references.citation: Growth Factors. 2006 Dec;24(4):268-78
references.pmid: 17381068
references.citation: J Orthop Res. 2008 Oct;26(10):1407-12
references.pmid: 18464249
references.citation: Int J Biochem Cell Biol. 2003 Sep;35(9):1323-40
references.pmid: 12798347
references.citation: Biomaterials. 2011 Jul;32(21):4793-805
references.pmid: 21489619
references.citation: Dev Biol. 2002 Oct 15;250(2):231-50
references.pmid: 12376100
references.citation: J Surg Res. 2004 Jun 1;119(1):85-91
references.pmid: 15126087
references.citation: J Biomed Mater Res. 2000 Jun 5;50(3):410-9
references.pmid: 10737884
references.citation: Nature. 2003 Oct 9;425(6958):577-84
references.pmid: 14534577
references.citation: Cell. 2008 Feb 22;132(4):511-3
references.pmid: 18295564
references.citation: Science. 1988 Dec 16;242(4885):1528-34
references.pmid: 3201241
references.citation: J Biochem. 2010 Jan;147(1):35-51
references.pmid: 19762341
references.citation: Bone. 2007 May;40(5):1389-98
references.pmid: 17303481
references.citation: Biomed Mater. 2015 Jul 23;10 (4):045008
references.pmid: 26201844
references.citation: J Cell Sci. 2007 Apr 1;120(Pt 7):1216-24
references.pmid: 17356069
references.citation: Cell Res. 2009 Jan;19(1):128-39
references.pmid: 19114990
references.citation: Kidney Int. 2000 Jun;57(6):2207-14
references.pmid: 10844590
references.citation: Bone. 2006 Oct;39(4):678-83
references.pmid: 16765663
references.citation: Osteoarthritis Cartilage. 2006 Nov;14(11):1126-35
references.pmid: 16765606
references.citation: Spine J. 2011 Jun;11(6):471-91
references.pmid: 21729796
references.citation: J Cell Biochem. 2003 Dec 15;90(6):1112-27
references.pmid: 14635186
references.citation: Biomaterials. 2013 Dec;34(38):9917-25
references.pmid: 24054499
references.citation: Biomaterials. 2009 Feb;30(5):763-9
references.pmid: 19036434
references.citation: Dev Biol. 1994 Jan;161(1):218-28
references.pmid: 8293874
references.citation: Cell Signal. 2004 Mar;16(3):291-9
references.pmid: 14687659
references.citation: Nature. 1999 Aug 12;400(6745):687-93
references.pmid: 10458166
references.citation: Biochem Biophys Res Commun. 2012 Mar 9;419(2):142-7
references.pmid: 22266317
references.citation: Nature. 2003 May 15;423(6937):316-8
references.pmid: 12748648
references.citation: J Bone Joint Surg Am. 1999 Jul;81(7):905-17
references.pmid: 10428121
references.citation: J Am Acad Orthop Surg. 2000 May-Jun;8(3):180-9
references.pmid: 10874225
references.citation: Development. 1996 Oct;122(10):2977-86
references.pmid: 8898212
references.citation: Cell Signal. 2011 Apr;23(4):609-20
references.pmid: 20959140
references.citation: J Bone Miner Res. 1996 Mar;11(3):312-24
references.pmid: 8852942
references.citation: J Oral Implantol. 1996;22(3-4):210-5
references.pmid: 9524496
references.citation: Am J Pathol. 2004 Mar;164(3):841-7
references.pmid: 14982838
references.citation: Exp Cell Res. 1996 Jan 10;222(1):38-47
references.pmid: 8549671
references.citation: Int Orthop. 2012 Mar;36(3):683; author reply 685
references.pmid: 22052478
references.citation: Trends Cell Biol. 2010 May;20(5):244-56
references.pmid: 20188563
references.citation: Calcif Tissue Int. 2001 Feb;68(2):87-94
references.pmid: 11310352
references.citation: Res Vet Sci. 2013 Dec;95(3):1210-6
references.pmid: 24054973
references.citation: Exp Cell Res. 2001 Aug 15;268(2):189-200
references.pmid: 11478845
references.citation: Br J Pharmacol. 2013 Dec;170(8):1676-705
references.pmid: 24528241
references.citation: Clin Plast Surg. 1994 Jul;21(3):429-35
references.pmid: 7924141
references.citation: Calcif Tissue Int. 1998 Oct;63(4):357-60
references.pmid: 9744997
references.citation: Exp Cell Res. 1999 Sep 15;251(2):264-74
references.pmid: 10471312
references.citation: Arthritis Res Ther. 2007;9(3):213
references.pmid: 17561986
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7632-6
references.pmid: 7644468
references.citation: Bone. 1998 Jun;22(6):591-603
references.pmid: 9626397
references.citation: Clin Orthop Relat Res. 1969 May-Jun;64:45-63
references.pmid: 4894527
references.citation: Biochem Biophys Res Commun. 2004 Jul 30;320(3):914-9
references.pmid: 15240135
references.citation: Neurosurgery. 2009 Dec;65(6 Suppl):75-81; discussion 81-3
references.pmid: 19935005
references.citation: Biochem Biophys Res Commun. 2006 Apr 14;342(3):902-8
references.pmid: 16500625
references.citation: Tissue Eng Part A. 2009 Jun;15(6):1311-20
references.pmid: 18950289
references.citation: Nat Genet. 1996 Jul;13(3):347-9
references.pmid: 8673135
references.citation: Mech Dev. 1995 Mar;50(1):71-83
references.pmid: 7605753
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: Cell. 2006 Aug 25;126(4):677-89
references.pmid: 16923388
references.citation: J Cell Biol. 2004 Jan 19;164(2):291-300
references.pmid: 14718519
references.citation: Exp Cell Res. 1998 Jan 10;238(1):265-72
references.pmid: 9457080
references.citation: Sci Signal. 2010 Feb 02;3(107):mr1
references.pmid: 20124549
references.citation: Nat Genet. 2006 Dec;38(12):1424-9
references.pmid: 17099713
references.citation: Nanomedicine (Lond). 2015;10(5):753-63
references.pmid: 25816878
references.citation: Biochem Biophys Res Commun. 2007 Oct 26;362(3):550-3
references.pmid: 17719560
references.citation: J Biomed Mater Res A. 2010 Aug;94(2):433-41
references.pmid: 20186742
references.citation: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 May;105(5):e14-24
references.pmid: 18442730
references.citation: Arthritis Res Ther. 2008;10(5):223
references.pmid: 18947375
references.citation: J Orthop Res. 1999 Mar;17(2):269-78
references.pmid: 10221845
references.citation: Nat Cell Biol. 2000 Aug;2(8):559-62
references.pmid: 10934479
references.citation: Cell Tissue Res. 2005 May;320(2):269-76
references.pmid: 15778851