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Published on: February 24, 2017
GDF15 enhances proliferation of aged chondrocytes by phosphorylating SMAD2
Dongming Wang1, Xiaochun Wei1, Xiang Geng2
1Department of Orthopedics, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China.
Background:
Aging is one of the primary factors influencing development of osteoarthritis, and the TGF-β pathway plays an important role in age-related osteoarthritis. Specifically, GDF15 phosphorylates SMAD2/3 in the TGF-β pathway to inhibit cardiomyocyte hypertrophy, and promote proliferation of chondrocytes. However, age-dependent changes in the level of GDF15 are unclear, as is whether GDF15 phosphorylates SMAD2/3 in the TGF-β pathway to promote proliferation of old chondrocytes. This study, therefore, sought to examine the effect of various GDF15 concentrations on old chondrocyte proliferation.
Methods:
Serum and cartilage specimens of young adults and older adults were collected, and GDF15 expression was quantified. Human chondrocytes were then cultured following routine protocols, and different concentrations of recombinant human GDF15 or pSMAD2 inhibitor were added into the culture medium. After 48 h of culturing, the proliferation of chondrocytes was detected by EdU, and the expression MMP13, SMAD2, and pSMAD2 was detected in chondrocytes via western blot and qRT-PCR analysis.
Results:
The GDF15 content in serum and cartilage of young adults was higher than that of older adults (p < 0.05). The number of EdU-positive cells in the experimental group (containing recombinant human GDF15) was higher than that in the control group (medium only) (p < 0.05). Compared with the control group, chondrocytes in the experimental group showed increased pSMAD2 and type II collagen content (p < 0.05) and decreased MMP13 (p < 0.05), with no significant difference in SMAD2 content (p > 0.05). Moreover, no significant differences were observed between the control group and the TGF-β signaling inhibitor group. The gene expression level of each index was consistent with the protein expression level.
Conclusions:
The GDF15 content of serum and cartilage in young adults is higher than in older adults, and GDF15 functions to promote the proliferation of chondrocytes by phosphorylating SMAD2 in older individuals.
Insights
Growth differentiation factor 15 (GDF15) promotes old chondrocyte proliferation by phosphorylating SMAD2, despite lower GDF15 levels in older adults. This finding offers insights into age-related osteoarthritis and potential therapeutic targets.
Area of Science:
- Cell Biology
- Biochemistry
- Osteoarthritis Research
Background:
- Aging is a primary risk factor for osteoarthritis.
- The TGF-β pathway is crucial in age-related osteoarthritis.
- GDF15's role in chondrocyte proliferation and its age-dependent changes require clarification.
Purpose of the Study:
- To investigate age-dependent changes in GDF15 levels.
- To determine if GDF15 promotes old chondrocyte proliferation via SMAD2 phosphorylation.
- To examine GDF15's effect on chondrocyte proliferation and TGF-β pathway activation.
Main Methods:
- Quantified GDF15 expression in serum and cartilage from young and older adults.
- Cultured human chondrocytes and treated them with varying GDF15 concentrations or a pSMAD2 inhibitor.
- Assessed chondrocyte proliferation (EdU assay) and expression of MMP13, SMAD2, and pSMAD2 (Western blot, qRT-PCR).
Main Results:
- GDF15 levels were higher in young adults than in older adults.
- Recombinant GDF15 significantly increased chondrocyte proliferation, pSMAD2, and type II collagen expression.
- GDF15 treatment decreased MMP13 expression and did not alter SMAD2 levels, while TGF-β inhibitor showed no significant effect compared to control.
Conclusions:
- GDF15 levels are lower in older adults' serum and cartilage.
- GDF15 promotes chondrocyte proliferation in older individuals by phosphorylating SMAD2.
- These findings highlight GDF15's role in age-related osteoarthritis pathogenesis.
