title: Osteogenic inhibition in multiple myeloma.
abstract: OBJECTIVE
  Multiple myeloma (MM) is a plasma cell malignancy where plasma cells are increased in the bone marrow (BM) and usually do not enter peripheral blood, but produce harmful factors creating problems in these patients (e.g. malignant plasma cells over activate osteoclasts and inhibit osteoblasts with factors like RANKL and DKK). These factors are a main cause of bone lesion in MM patients. Recently SOST gene which responsible to encodes the sclerostin protein was identify. This protein specifically inhibits Wnt signaling in osteoblasts (inhibition of osteoblast differentiation and proliferation) and decrease bone formation and can also cause bone lesion in MM patients.
  
  
  METHODS
  In this experimental study, human myeloma cell lines (U266 b1) were purchased from Pasteur Institute of Iran. Samples consisted of BM aspirates from the iliac crest of MM patients. BM with more than 70% plasma cell were selected for our study (6 patients) and one healthy donor. RNA extraction was done with Qiagen kit. was undertaken on mRNA of samples and cell lines. Also we purchased unrestricted somatic stem cells from Bonyakhte Company to evaluate the effect of soluble factors from myeloma cell lines on osteogenic differentiation medium.
  
  
  RESULTS
  Our results showed that SOST is expressed significantly in primary myeloma cells derived from MM patients and myeloma cell lines. In other words, patients with more bone problems, express SOST in their plasma cells at a higher level. In addition, myeloma cells inhibit osteoblast differentiation in progenitor cells from umbilical cord blood stem cell (UCSC) in osteogenic inducing medium.
  
  
  CONCLUSIONS
  There are many osteoblast maturation inhibitory factors such as DKK, Sfrp and Sclerostin that inhibit maturation of osteoblast in bone. Among osteoblast inhibitory agents (DKK, Sfrp, Sclerostin) sclerostin has the highest specificity and therefore will have less side effect versus non-specific inhibitory agents. Our results also show that based on SOST expression in MM, there is a potential to inhibit sclerostin with antibody or alternative methods and prevent bone lesion in MM patients with the least side effect.
authors.affiliation: 1. Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Hussain
authors.initials: H
authors.lastname: Habibi
authors.forename: Saeid
authors.initials: S
authors.lastname: Abroun
authors.forename: Abbas
authors.initials: A
authors.lastname: Hajifathali
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.forename: Saeid
authors.initials: S
authors.lastname: Kaviani
authors.forename: Nasim
authors.initials: N
authors.lastname: Kalantari
authors.forename: Susan
authors.initials: S
authors.lastname: Eslahchi
keywords: Cord Blood Stem Cells; Multiple Myeloma; Osteoblast; SOST; Sclerostin
references.citation: Blood. 2005 Aug 15;106(4):1407-14
references.pmid: 15878977
references.citation: J Biol Chem. 2005 Sep 30;280(39):33132-40
references.pmid: 16043491
references.citation: J Musculoskelet Neuronal Interact. 2006 Oct-Dec;6(4):355-6
references.pmid: 17185822
references.citation: Dev Dyn. 2000 Dec;219(4):461-71
references.pmid: 11084646
references.citation: Blood. 2005 Oct 1;106(7):2472-83
references.pmid: 15933061
references.citation: J Clin Invest. 2006 May;116(5):1202-9
references.pmid: 16670761
references.citation: Curr Pharm Biotechnol. 2009 Apr;10(3):345-6
references.pmid: 19355944
references.citation: Circ Res. 2010 Jun 25;106(12):1798-806
references.pmid: 20576942
references.citation: Blood. 2006 Dec 15;108(13):3992-6
references.pmid: 16917004
references.citation: Eur J Cancer. 2006 Jul;42(11):1544-53
references.pmid: 16765040
references.citation: Cancer Res. 2007 Aug 15;67(16):7665-74
references.pmid: 17702698
references.citation: Blood Cancer J. 2011 Jun;1(6):e27
references.pmid: 22829171
references.citation: Blood. 2007 Aug 15;110(4):1098-104
references.pmid: 17494860
references.citation: Oncologist. 2009 Mar;14(3):276-83
references.pmid: 19286761
references.citation: J Musculoskelet Neuronal Interact. 2004 Jun;4(2):139-42
references.pmid: 15615113
references.citation: Ann Oncol. 2005 Aug;16(8):1223-31
references.pmid: 15928069
references.citation: J Bone Miner Res. 2008 Jun;23(6):860-9
references.pmid: 18269310
references.citation: Expert Opin Ther Targets. 2009 Apr;13(4):485-96
references.pmid: 19335070
references.citation: Blood. 2008 Mar 15;111(6):2962-72
references.pmid: 18332230
references.citation: Kobe J Med Sci. 2007;53(1-2):25-35
references.pmid: 17579299
references.citation: J Manag Care Pharm. 2008 Sep;14(7 Suppl):4-6
references.pmid: 18774879
references.citation: Clin Genet. 2003 Mar;63(3):192-7
references.pmid: 12694228
references.citation: J Cell Biochem. 2010 Feb 1;109(2):283-91
references.pmid: 20014067
references.citation: Blood. 2004 Mar 15;103(6):2308-15
references.pmid: 14615378
references.citation: Genome Res. 2005 Jul;15(7):928-35
references.pmid: 15965026
references.citation: Biol Blood Marrow Transplant. 2001;7(11):581-8
references.pmid: 11760145
references.citation: Gene. 2004 Oct 27;341:19-39
references.pmid: 15474285