A Stem Cell-Based Approach to Cartilage Repair

被引：623

作者：

Johnson, Kristen ^{[1
]}

Zhu, Shoutian ^{[2
]}

Tremblay, Matthew S. ^{[1
,2
]}

Payette, Joshua N. ^{[2
]}

Wang, Jianing ^{[2
]}

Bouchez, Laure C. ^{[2
]}

Meeusen, Shelly ^{[1
]}

Althage, Alana ^{[1
]}

Cho, Charles Y. ^{[1
]}

Wu, Xu ^{[3
]}

Schultz, Peter G. ^{[2
]}

机构：

[1] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

[2] Scripps Res Inst, La Jolla, CA 92037 USA

[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

来源：

SCIENCE | 2012年 / 336卷 / 6082期

关键词：

ARTICULAR-CARTILAGE; CHONDROCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; OSTEOARTHRITIS; BONE; PATHOGENESIS; FILAMIN; GENE; CHONDROGENESIS; EXPRESSION;

D O I：

10.1126/science.1215157

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor beta subunit (CBF beta), and induces chondrogenesis by regulating the CBF beta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis.

引用

页码：717 / 721

页数：5

共 35 条

[1] Function of CBFβ/Bro proteins [J].

Adya, N ;

Castilla, LH ;

Liu, PP .

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2000, 11 (05) :361-368

[2] Bone Marrow Mesenchymal Stem Cells: Historical Overview and Concepts [J].

Charbord, Pierre .

HUMAN GENE THERAPY, 2010, 21 (09) :1045-1056

[3]

Coluet J, 2009, DRUG DISCOV TODAY, V14, P913, DOI 10.1016/j.drudis.2009.07.012

[4] Interactions between integrin ligand density and cytoskeletal integrity regulate BMSC chondrogenesis [J].

Connelly, John T. ;

Garcia, Andres J. ;

Levenston, Marc E. .

JOURNAL OF CELLULAR PHYSIOLOGY, 2008, 217 (01) :145-154

[5] Identification of novel protein/DNA interactions within the promoter of the bone-related transcription factor Runx2/Cbfa1 [J].

Drissi, H ;

Pouliot, A ;

Stein, JL ;

van Wijnen, AJ ;

Stein, GS ;

Lian, JB .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2002, 86 (02) :403-412

[6] The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse [J].

Glasson, S. S. ;

Blanchet, T. J. ;

Morris, E. A. .

OSTEOARTHRITIS AND CARTILAGE, 2007, 15 (09) :1061-1069

[7] Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis [J].

Goldring, Mary B. ;

Goldring, Steven R. .

SKELETAL BIOLOGY AND MEDICINE, 2010, 1192 :230-237

[8] HUMAN ENDOTHELIAL ACTIN-BINDING PROTEIN (ABP-280, NONMUSCLE FILAMIN) - A MOLECULAR LEAF SPRING [J].

GORLIN, JB ;

YAMIN, R ;

EGAN, S ;

STEWART, M ;

STOSSEL, TP ;

KWIATKOWSKI, DJ ;

HARTWIG, JH .

JOURNAL OF CELL BIOLOGY, 1990, 111 (03) :1089-1105

[9] Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis [J].

Grogan, Shawn P. ;

Miyaki, Shigeru ;

Asahara, Hiroshi ;

D'Lima, Darryl D. ;

Lotz, Martin K. .

ARTHRITIS RESEARCH & THERAPY, 2009, 11 (03)

[10] Pharmacologic therapy for osteoarthritis-the era of disease modification [J].

Hunter, David J. .

NATURE REVIEWS RHEUMATOLOGY, 2011, 7 (01) :13-22

← 1 2 3 4 →