Positive Effects of a Young Systemic Environment and High Growth Differentiation Factor 11 Levels on Chondrocyte Proliferation and Cartilage Matrix Synthesis in Old Mice

Autor: Xiaochun Wei, Pengcui Li, Dongming Wang, Zhi Lv, Lu Li, Kaihang Wang, Xiang Geng, Jian Sun, Jiangong Lu, Xiaoming Cao, Lei Wei, Xiaohu Wang
Rok vydání: 2019
Předmět:
0301 basic medicine
Cartilage
Articular
Male
Aging
Knee Joint
Core Binding Factor Alpha 1 Subunit
Osteoarthritis
Smad2 Protein
Mice
0302 clinical medicine
Immunology and Allergy
Phosphorylation
Arthroplasty
Replacement
Knee
Chemistry
Reverse Transcriptase Polymerase Chain Reaction
SOX9 Transcription Factor
Osteoarthritis
Knee
Stifle
Extracellular Matrix
Growth Differentiation Factors
medicine.anatomical_structure
Bone Morphogenetic Proteins
Female
medicine.medical_specialty
Adolescent
Parabiosis
Immunology
Type II collagen
In Vitro Techniques
Chondrocyte
03 medical and health sciences
Young Adult
Chondrocytes
Rheumatology
In vivo
Internal medicine
Matrix Metalloproteinase 13
medicine
Animals
Humans
RNA
Messenger
Smad3 Protein
Collagen Type II
Aged
Cell Proliferation
030203 arthritis & rheumatology
Cartilage
Histology
medicine.disease
030104 developmental biology
Endocrinology
GDF11
Collagen Type X
Zdroj: Arthritisrheumatology (Hoboken, N.J.)References. 72(7)
ISSN: 2326-5205
Popis: OBJECTIVE To investigate the effects of a young systemic environment and growth differentiation factor 11 (GDF-11) on aging cartilage. METHODS A heterochronic parabiosis model (2-month-old mouse and 12-month-old mouse [Y/O]), an isochronic parabiosis model (12-month-old mouse and 12-month-old mouse [O/O]), and 12-month-old mice alone (O) were evaluated. Knee joints and chondrocytes from old mice were examined by radiography, histology, cell proliferation assays, immunohistochemistry, Western blotting, and quantitative reverse transcriptase-polymerase chain reaction 16 weeks after parabiosis surgery. GDF-11 was injected into 12-month-old mouse joints daily for 16 weeks. Cartilage degeneration, cell proliferation, and osteoarthritis-related gene expression were evaluated. RESULTS Osteoarthritis Research Society International scores in old mice were significantly lower in the Y/O group than in the O/O and O groups (both P < 0.05). The percentage of 5-ethynyl-2'-deoxyuridine-positive chondrocytes in old mice was significantly higher in the Y/O group than in the other groups (P < 0.05). Type II collagen (CII) and SOX9 messenger RNA levels differed in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). RUNX-2, CX, and matrix metalloproteinase 13 levels were significantly lower in cartilage from old mice in the Y/O group compared to the O/O and O groups (both P < 0.05). Similar results were obtained for protein expression levels and after GDF-11 treatment in vitro and in vivo. Phosphorylated Smad2/3 (pSmad2/3) levels were higher in the recombinant GDF-11-treated group than in the control group. CONCLUSION A young systemic environment promotes chondrocyte proliferation and cartilage matrix synthesis in old mice. GDF-11, a "young factor," contributes to these effects through the up-regulation of pSmad2/3.
Databáze: OpenAIRE
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