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Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression.

ABSTRACT: Intra-articular injection of mesenchymal stem cells (MSCs) is a promising strategy for osteoarthritis (OA) treatment. However, more and more studies reveal that the injected MSCs have poor adhesion, migration, and survival in the joint cavity. A recent study shows that tropoelastin (TE) regulates adhesion, proliferation and phenotypic maintenance of MSCs as a soluble additive, indicating that TE could promote MSCs-homing in regenerative medicine. In this study, we used TE as injection medium, and compared it with classic media in MSCs intra-articular injection such as normal saline (NS), hyaluronic acid (HA), and platelet-rich plasma (PRP). We found that TE could effectively improve adhesion, migration, chondrogenic differentiation of infrapatellar fat pad MSCs (IPFP-MSCs) and enhance matrix synthesis of osteoarthritic chondrocytes (OACs) in indirect-coculture system. Moreover, TE could significantly enhance IPFP-MSCs adhesion via activation of integrin β1, ERK1/2 and vinculin (VCL) in vitro. In addition, intra-articular injection of TE-IPFP MSCs suspension resulted in a short-term increase in survival rate of IPFP-MSCs and better histology scores of rat joint tissues. Inhibition of integrin β1 or ERK1/2 attenuated the protective effect of TE-IPFP MSCs suspension in vivo. In conclusion, TE promotes performance of IPFP-MSCs and protects knee cartilage from damage in OA through enhancement of cell adhesion and activation of integrin β1/ERK/VCL pathway. Our ﬁndings may provide new insights in MSCs intra-articular injection for OA treatment.

SUBMITTER: Yang J

PROVIDER: S-EPMC8636741 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort. All knees had a Kellgren-Lawrence grade of 1 or less at baseline. During the 4-year follow-up, case participants were matched 1:1 to control participants, with incident radiographic KOA as the outcome. MRI scans were segmented at the incident time point of KOA (hereafter, P0), 1 year before P0 (hereafter, P-1), and baseline. MRI-based three-dimensional texture analysis was performed to extract IPFP texture features. Least absolute shrinkage and selection operator and multivariable logistic regressions were applied in the development cohort and evaluated in the test cohort. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative value of the clinical score, IPFP texture score, and MRI Osteoarthritis Knee Score. Results Participants were allocated to development (n = 500, 340 women; mean age, 60 years) and test (n = 190, 120 women; mean age, 61 years) cohorts. In both cohorts, IPFP texture scores (AUC ≥0.75 for all) showed greater discrimination than clinical scores (AUC ≤0.69 for all) at baseline, P-1, and P0, with significant differences in pairwise comparisons (P ≤ .002 for all). Greater predictive and concurrent validities of IPFP texture scores (AUC ≥0.75 for all) compared with MRI Osteoarthritis Knee Scores (AUC ≤0.66 for all) were also demonstrated (P < .001 for all). Conclusion MRI-based three-dimensional texture of the infrapatellar fat pad was associated with future development of knee osteoarthritis. ClinicalTrials.gov registration no.: NCT00080171 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Fischer in this issue.

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Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression.

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