Advances in Stem Cell-Based Therapies in the Treatment of Osteoarthritis

Chen, Ye; Cheng, Rui-Juan; Wu, Yinlan; Huang, Deying; Li, Yanhong; Liu, Yi

doi:10.3390/ijms25010394

Cited by 3 publications

(1 citation statement)

References 128 publications

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“…Its GO terms focus on functions such as protein synthesis and transportation, adding that representative genes of catabolism such as MMP3 are specifically expressed in this subtype, indicating that this subtype is a group of chondrocytes with active synthesis and catabolism process. The balance between synthesis and catabolism in chondrocytes is the driving force for cartilage tissue to maintain and renew its ECM ( 19 , 20 ). Moreover, previous research has demonstrated the potential of METRNL in mitigating inflammation and pyroptosis in osteoarthritis ( 21 ), combined with METRNL+ subtype mainly comes from healthy cartilage, which suggest the cartilage protective effect of this subtype.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals different chondrocyte states in femoral cartilage between osteoarthritis and healthy individuals

Sun,

Yan,

Wang

et al. 2024

Front. Immunol.

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BackgroundCartilage injury is the main pathological manifestation of osteoarthritis (OA). Healthy chondrocyte is a prerequisite for cartilage regeneration and repair. Differences between healthy and OA chondrocyte types and the role these types play in cartilage regeneration and OA progression are unclear.MethodThis study conducted single-cell RNA sequencing (scRNA-seq) on the cartilage from normal distal femur of the knee (NC group) and OA femur (OA group) cartilage, the chondrocyte atlas was constructed, and the differences of cell subtypes between the two groups were compared. Pseudo-time and RNA velocity analysis were both performed to verify the possible differentiation sequence of cell subtypes. GO and KEGG pathway enrichment analysis were used to explore the potential functional characteristics of each cell subtype, and to predict the functional changes during cell differentiation. Differences in transcriptional regulation in subtypes were explored by single-cell regulatory network inference and clustering (SCENIC). The distribution of each cell subtype in cartilage tissue was identified by immunohistochemical staining (IHC).ResultA total of 75,104 cells were included, they were divided into 19 clusters and annotated as 11 chondrocyte subtypes, including two new chondrocyte subtypes: METRNL+ and PRG4+ subtype. METRNL+ is in an early stage during chondrocyte differentiation, and RegC-B is in an intermediate state before chondrocyte dedifferentiation. With cell differentiation, cell subtypes shift from genetic expression to extracellular matrix adhesion and collagen remodeling, and signal pathways shift from HIF-1 to Hippo. The 11 subtypes were finally classified as intrinsic chondrocytes, effector chondrocytes, abnormally differentiated chondrocytes and dedifferentiated chondrocytes. IHC was used to verify the presence and distribution of each chondrocyte subtype.ConclusionThis study screened two new chondrocyte subtypes, and a novel classification of each subtype was proposed. METRNL+ subtype is in an early stage during chondrocyte differentiation, and its transcriptomic characteristics and specific pathways provide a foundation for cartilage regeneration. EC-B, PRG4+ RegC-B, and FC are typical subtypes in the OA group, and the HippO-Taz pathway enriched by these cell subtypes may play a role in cartilage repair and OA progression. RegC-B is in the intermediate state before chondrocyte dedifferentiation, and its transcriptomic characteristics may provide a theoretical basis for intervening chondrocyte dedifferentiation.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals different chondrocyte states in femoral cartilage between osteoarthritis and healthy individuals

Sun,

Yan,

Wang

et al. 2024

Front. Immunol.

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FGF18 encoding circular mRNA-LNP based on glycerolipid engineering of mesenchymal stem cells for efficient amelioration of osteoarthritis

Huang,

Liu,

Qin

et al. 2024

Biomater. Sci.

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Quadriceps recovery and pain relief in knee osteoarthritis rats by cog polydioxanone filament insertion

Cha,

Bak,

Bai

et al. 2024

Regenerative Biomaterials

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Quadriceps muscles play a pivotal role in knee osteoarthritis (OA) progression and symptom manifestation, particularly pain. This research investigates the therapeutic effectiveness of muscle enhancement and support therapy (MEST), a recently developed device intended for intramuscular insertion of cog polydioxanone filaments, in quadriceps restoration to alleviate OA pain. Knee OA was induced in Sprague Dawley rats via monoiodoacetate injections. MEST or sham treatment was performed in OA or Naive rat quadriceps. Pain was assessed using paw withdrawal threshold and weight bearing. Quadriceps injury and recovery via MEST were evaluated using biomarkers, tissue morphology, muscle mass, contractile force and hindlimb torque. Satellite cell and macrophage activation, along with their activators, were also assessed. Data were compared at 1- and 3-weeks post-MEST treatment (M-W1 and M-W3). MEST treatment in OA rats caused muscle injury, indicated by elevated serum aspartate transferase and creatinine kinase levels, and local β-actin changes at M-W1. This injury triggered pro-inflammatory macrophage and satellite cell activation, accompanied by heightened interleukin-6 and insulin-like growth factor-1 levels. However, by M-W3, these processes gradually shifted toward inflammation resolution and muscle restoration. This was seen in anti-inflammatory macrophage phenotypes, sustained satellite cell activation and injury markers regressing to baseline. Quadriceps recovery in mass and strength from atrophy correlated with substantial OA pain reduction at M-W3. This study suggests that MEST-induced minor muscle injury triggers macrophage and satellite cell activation, leading to recovery of atrophied quadriceps and pain relief in OA rats.

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Advances in Stem Cell-Based Therapies in the Treatment of Osteoarthritis

Cited by 3 publications

References 128 publications

Single-cell RNA sequencing reveals different chondrocyte states in femoral cartilage between osteoarthritis and healthy individuals

Single-cell RNA sequencing reveals different chondrocyte states in femoral cartilage between osteoarthritis and healthy individuals

FGF18 encoding circular mRNA-LNP based on glycerolipid engineering of mesenchymal stem cells for efficient amelioration of osteoarthritis

Quadriceps recovery and pain relief in knee osteoarthritis rats by cog polydioxanone filament insertion

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