Muscle cell-derived factors inhibit inflammatory stimuli-induced damage in hMSC-derived chondrocytes

Autor: Heenam Kwon, Rucsanda C. Preda, Roshni S. Rainbow, David L. Kaplan, Andrea T. Foote, Li Zeng
Rok vydání: 2013
Předmět:
Pathology
medicine.medical_specialty
Interleukin-1beta
Biomedical Engineering
Gene Products
gag
Apoptosis
Cell Cycle Proteins
Core Binding Factor Alpha 1 Subunit
Stem cells
Pro-inflammatory
Cartilage tissue engineering
Article
Chondrocyte
Myoblasts
03 medical and health sciences
Chondrocytes
0302 clinical medicine
Rheumatology
Osteoarthritis
medicine
Humans
Myocyte
Orthopedics and Sports Medicine
Aggrecans
Collagen Type II
Cell Proliferation
030304 developmental biology
030203 arthritis & rheumatology
0303 health sciences
Caspase 3
Tumor Necrosis Factor-alpha
Cartilage homeostasis
Chemistry
Cartilage
Mesenchymal stem cell
Mesenchymal Stem Cells
Fibroblasts
Chondrogenesis
Matrix Metalloproteinases
Cell biology
Ki-67 Antigen
medicine.anatomical_structure
Case-Control Studies
Cytokines
Myokines
Stem cell
C2C12
Collagen Type X
Zdroj: Osteoarthritis and Cartilage. 21:990-998
ISSN: 1063-4584
Popis: Summary Objective Pro-inflammatory cytokines play an important role in inducing cartilage degradation during osteoarthritis pathogenesis. Muscle is a tissue that lies near cartilage in situ . However, muscle's non-loading biochemical effect on cartilage has been largely unexplored. Here, we tested the hypothesis that muscle cells can regulate the response to pro-inflammatory cytokine-mediated damage in chondrocytes derived from human bone marrow-derived mesenchymal stem cells (hMSCs). Method hMSCs were allowed to undergo chondrogenic differentiation in porous silk scaffolds in the typical chondrogenic medium for 12 days. For the next 9 days, the cells were cultured in chondrogenic medium containing 50% conditioned medium derived from C2C12 muscle cells or fibroblast control cells, and were subject to treatments of pro-inflammatory cytokines IL-1β or TNFα. Results Both IL-1β and TNFα-induced strong expression of multiple MMPs and hypertrophic markers Runx2 and type X collagen. Strikingly, culturing hMSC-derived chondrocytes in C2C12 muscle cell-conditioned medium strongly inhibited the expression of all these genes, a result further confirmed by GAG content and histological evaluation of matrix protein. To determine whether these effects were due to altered chondrocyte growth and survival, we assayed the expression of cell proliferation marker Ki67, cell cycle arrest markers p21 and p53, and apoptosis marker caspase 3. Muscle cell-conditioned medium promoted proliferation and inhibited apoptosis, thereby suggesting a possible decrease in the cellular aging and death that typically accompanies cartilage inflammation. Conclusion Our findings suggest the role of muscle in cartilage homeostasis and provide insight into designing strategies for promoting resistance to pro-inflammatory cytokines in hMSC-derived chondrocytes.
Databáze: OpenAIRE
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