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Updated: Jan 31, 2026

Differentiating Chondrocytes from Peripheral Blood-derived Human Induced Pluripotent Stem Cells
Published on: July 18, 2017
Recombinant growth differentiation factor 11 impairs fracture healing through inhibiting chondrocyte differentiation
Rixin Zheng1, Liang Xie1, Weiqing Liu1
1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Abstract:
Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor-β (TGF-β) superfamily, has been reported to have the capacity to reverse age-related pathologic changes and regulate organ regeneration after injury; however, the role of GDF11 in fracture healing and bone repair is still unclear. Here, we established a fracture model in 12-week-old male mice to observe two healing states: the cartilaginous callus and bony callus formation phases. Our results showed that recombinant GDF11 (rGDF11) injection inhibits cartilaginous callus maturation and hard callus formation, thereby impairing fracture healing in vivo. In vitro, rGDF11 administration inhibited chondrocyte differentiation and maturation by phosphorylating SMAD2/3 protein and inhibiting RUNX2 expression. Notably, inhibition of TGF-β activity by a SMAD-specific inhibitor attenuated GDF11 effects. Thus, our study demonstrates that, rather than acting as a rejuvenating agent, rGDF11 impairs fracture healing by inhibiting chondrocyte differentiation and maturation.
Insights
Growth differentiation factor 11 (GDF11) impairs fracture healing by inhibiting chondrocyte maturation and bone repair. This study reveals GDF11
Area of Science:
- Biochemistry
- Cell Biology
- Regenerative Medicine
Background:
- Growth differentiation factor 11 (GDF11) is a TGF-β superfamily member with reported rejuvenating properties.
- Its specific role in fracture healing and bone repair remains largely uncharacterized.
Purpose of the Study:
- To investigate the effect of GDF11 on fracture healing and bone repair processes.
- To elucidate the underlying molecular mechanisms of GDF11's action in bone regeneration.
Main Methods:
- Established a fracture model in 12-week-old male mice.
- Administered recombinant GDF11 (rGDF11) and observed fracture healing stages (cartilaginous and bony callus).
- Performed in vitro studies on chondrocytes, assessing differentiation and maturation markers, including SMAD2/3 phosphorylation and RUNX2 expression.
Main Results:
- rGDF11 injection significantly inhibited cartilaginous callus maturation and hard callus formation, impairing fracture healing in vivo.
- In vitro, rGDF11 suppressed chondrocyte differentiation and maturation.
- These effects were mediated by SMAD2/3 phosphorylation and RUNX2 inhibition, and were attenuated by a SMAD-specific inhibitor.
Conclusions:
- Contrary to expectations, GDF11 does not promote fracture healing and acts as an inhibitor.
- GDF11 impairs bone repair by hindering chondrocyte differentiation and maturation through TGF-β signaling pathways.
- GDF11 is not a rejuvenating agent for fracture healing.
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