Journal article
Chondrogenic Progenitor Cells Promote Vascular Endothelial Growth Factor Expression Through Stromal-derived Factor-1
Osteoarthritis and cartilage, Vol.25(5), pp.742-749
05/2017
DOI: 10.1016/j.joca.2016.10.017
PMCID: PMC6367939
PMID: 27989872
Abstract
Objective: Vascular endothelial growth factor (VEGF) is elevated in joint fluids from patients diagnosed with osteoarthritis (OA). VEGF is known to contribute to vascular tidemark invasion and osteophyte formation, which are classic features of advanced OA. Among the factors that may drive VEGF accumulation in diseased joints, stromal cell-derived factor-1α (SDF-1α) is a likely culprit, as it is enriched in synovial fluids from osteoarthritic joints and is a potent inducer of VEGF expression. Chondrogenic progenitor cells (CPCs) that overexpress SDF-1α are abundant in osteoarthritic cartilage, implicating them in elevating synovial SDF-1α levels. Here we conducted a series of experiments to determine the potential for CPCs to stimulate VEGF expression via autocrine and paracrine mechanisms.
Design: Immunohistochemistry, immunoblotting, and PCR were used to evaluate the effects of SDF-1α on VEGF expression in CPCs and chondrocytes, and the effects of CPC-conditioned medium on chondrocytes. An SDF-1α receptor antagonist and inhibitors of mitogen-activated protein kinases (MAPKs) were used to probe the pathway linking SDF-1 with VEGF expression in CPCs.
Results: SDF-1α and CPC-conditioned medium stimulated VEGF expression in chondrocytes. In both chondrocytes and CPCs, SDF-1α stimulated increased VEGF expression via C-X-C chemokine receptor type 4 (CXCR4), a cell-surface SDF-1α receptor. This response in CPCs is dependent on p38 MAPK activation, but not on ERK or c-Jun N-terminal kinase (JNK) activation.
Conclusions: By secreting SDF-1α, CPCs stimulate VEGF expression in nearby cells. The co-expression of SDF-1 and its receptor by CPCs indicates they are capable of self-sustained VEGF expression via an autocrine mechanism.
Details
- Title: Subtitle
- Chondrogenic Progenitor Cells Promote Vascular Endothelial Growth Factor Expression Through Stromal-derived Factor-1
- Creators
- Shuya Wang - Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, Harbin China, 150001Cheng Zhou - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IAHongjun Zheng - Department of Orthopaedic Surgery, Washington University, St. Louis, MOZhiyi Zhang - Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, Harbin China, 150001YiFang Mei - Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, Harbin China, 150001James A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Osteoarthritis and cartilage, Vol.25(5), pp.742-749
- DOI
- 10.1016/j.joca.2016.10.017
- PMID
- 27989872
- PMCID
- PMC6367939
- ISSN
- 1063-4584
- eISSN
- 1522-9653
- Grant note
- name: US DHHS; DOI: 10.13039/100000002, name: National Institutes of Health, award: 5 P50 AR055533; DOI: 10.13039/100000069, name: NIAMS; DOI: 10.13039/100008893, name: University of Iowa Department of Orthopedics and Rehabilitation; name: US DHHS; DOI: 10.13039/100000002, name: National Institutes of Health, award: 5 P50 AR055533; DOI: 10.13039/100000069, name: NIAMS; DOI: 10.13039/100008893, name: University of Iowa Department of Orthopedics and Rehabilitation
- Language
- English
- Date published
- 05/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation
- Record Identifier
- 9984040257802771
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