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Updated: Jul 6, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral
Xiao-Tong Li1,2, Zhi-Ling Li1,2, Pei-Lin Li1,2
1Department of Stem Cells and Regenerative Medicine, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.
Abstract:
Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.
Insights
Skeletal stem cells (SSCs) can treat osteoarthritis (OA) by preventing the death of bone cells. SSCs-derived TNFAIP3 is key to this protective effect, offering a new therapeutic target for OA.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) involves joint tissue cell death, specifically necroptosis.
- Subchondral osteoblasts play a critical role in OA pathogenesis.
Purpose of the Study:
- To investigate the effect of exogenous skeletal stem cells (SSCs) on subchondral osteoblast necroptosis in OA.
- To identify the molecular mechanisms by which SSCs exert their protective effects.
Main Methods:
- Utilized human SSCs and subchondral osteoblasts in vitro.
- Employed Western blotting, real-time PCR, RNA sequencing, and gene editing.
- Validated findings in a rat anterior cruciate ligament transection OA model.
Main Results:
- Intra-articular SSC injections improved subchondral bone microarchitecture in OA rats.
- SSCs significantly inhibited subchondral osteoblast necroptosis both in vivo and in vitro.
- SSCs-derived TNFAIP3 was identified as a key mediator in suppressing osteoblast necroptosis.
Conclusions:
- SSCs suppress subchondral osteoblast necroptosis in OA through TNFAIP3.
- TNFAIP3-overexpressing SSCs enhanced therapeutic effects in OA rats.
- Targeting necroptotic osteoblasts via stem cell therapy presents a promising strategy for OA treatment.
