Bone morphogenetic protein 2 stimulates chondrogenesis of equine synovial membrane-derived progenitor cells

Yuwen Chen; Evelyn Caporali; Matthew Stewart

doi:10.3415/VCOT-16-02-0035

Veterinary and Comparative Orthopaedics and Traumatology, Inhaltsverzeichnis

Vet Comp Orthop Traumatol 2016; 29(05): 378-385
DOI: 10.3415/VCOT-16-02-0035

Original Research

Schattauer GmbH

Bone morphogenetic protein 2 stimulates chondrogenesis of equine synovial membrane-derived progenitor cells

Yuwen Chen

¹Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA

²Current address: QPS Taiwan, Center of Toxicology and Preclinical Sciences, Xizhi Dist., New Taipei City, Taiwan

,

Evelyn Caporali

¹Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA

³Current address: Coral Springs Animal Hospital, Coral Springs, FL, USA

,

Matthew Stewart

¹Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA

› Institutsangaben

Abstract

Summary

Objectives: Bone morphogenetic protein 2 (BMP-2) is critical for skeletal and cartilage development, homeostasis and repair. This study was conducted to clone and characterize equine BMP-2, develop expression constructs for equine BMP-2, and to determine whether BMP-2 can stimulate chondrogenesis of equine synovial membrane-derived progenitor cells (SMPC).

Methods: Equine BMP-2 cDNA was amplified from chondrocyte RNA, and then transferred into an expression plasmid and adenoviral vector. Effective expression of equine BMP-2 was confirmed using a BMP reporter cell line. SMPC were isolated from synovium, expanded through two passages and transferred to chondrogenic cultures, with recombinant human (rh) transforming growth factor beta 1 (TGF-[uni03B2]1) or rhBMP-2. Chondro-genesis was assessed by up-regulation of collagen types II and X, and aggrecan mRNA, secretion of collagen type II protein and sulfated glycosaminoglycans (sGAG), and by alkaline phosphatase induction. Chondrogenic stimulation of SMPC by the equine BMP-2 adenovirus was assessed by sGAG secretion and histology.

Results: The mature equine BMP-2 peptide is identical to human and murine peptides. Recombinant human BMP-2 and TGF-[uni03B2]1 stimulated equivalent amounts of collagen type II protein in SMPC pellets, but sGAG secretion was doubled by BMP-2. Neither factor stimulated hypertrophic marker expression. The equine BMP-2 adenoviral vector induced chondrogenesis comparably to rhBMP-2 protein, with no indication of hypertrophy.

Clinical significance: Bone morphogenetic protein 2 is a potent inducer of SMPC nonhypertrophic chondrogenesis, supporting the use of this combination for articular cartilage repair applications.

Keywords

Equine BMP-2 - bone morphogenetic protein 2 - synovial membrane progenitor - chondro-genesis - adenoviral vector

Volltext

Referenzen

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