title: Methylsulfonylmethane enhances BMP‑2‑induced osteoblast differentiation in mesenchymal stem cells.
abstract: As human lifespans have increased, the incidence of osteoporosis has also increased. Methylsulfonylmethane (MSM) affects the process of mesenchymal stem cell (MSC) differentiation into osteoblasts via the Janus kinase 2 (Jak2)/signal transducer and activator of transcription (STAT)5b signaling pathway, and bone morphogenetic protein 2 (BMP‑2) is also known to significantly affect bone health. In addition, the phosphorylation of small mothers against decapentaplegic (Smad)1/5/8 regulates the Runt‑related transcription factor 2 (Runx2) gene, which encodes a transcription factor for osteoblast differentiation markers. In the present study, the differentiation of MSCs treated with MSM, BMP‑2, and their combination were examined. The differentiation of osteoblasts was demonstrated through observation of morphological changes and mineralization, using alizarin red and Von Kossa staining. Western blotting analysis demonstrated that the combination of MSM and BMP-2 increased the phosphorylation of the BMP signaling-associated protein, Smad1/5/8. Combination of MSM and BMP-2 significantly increased osteogenic differentiation and mineralization of the MSCs compared with either MSM or BMP-2 alone. Additionally, reverse transcription-polymerase chain reaction analysis demonstrated that combination of MSM and BMP-2 increased the expression level of the Runx2 gene and the osteoblast differentiation marker genes, alkaline phosphatase, bone sialoprotein and osteocalcin, in MSCs compared with controls. Thus, the combination of MSM and BMP-2 may promote the differentiation of MSCs into osteoblasts.
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Don Nam
authors.initials: DN
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Joung
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Pramod
authors.initials: P
authors.lastname: Darvin
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Kang
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Nipin
authors.initials: N
authors.lastname: Sp
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Hyo Joo
authors.initials: HJ
authors.lastname: Byun
authors.affiliation: National Institute of Animal Science, RDA, Cheonan 331‑801, Republic of Korea.
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Genomics Informatics Center, Hankyong National University, Anseong 456‑749, Republic of Korea.
authors.forename: Kyung Do
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Animal Biotechnology, Chonbuk National University, Jeonju 561‑756, Republic of Korea.
authors.forename: Hak Kyo
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Young Mok
authors.initials: YM
authors.lastname: Yang
mesh_terms: D000818:Animals; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; D013450:Sulfones; C025910:dimethyl sulfone; D004121:Dimethyl Sulfoxide