Abstract
SummaryAIM:The aim of this study was to investigate whether an aged systemic environment could impair young cartilage tissue in mice.METHODS:Mice differing in age were randomly divided into three groups. Group 1 was the experimental group (Y/O group) consisting of the heterochronic parabiosis model (2-month-old/12-month-old, young/old). Group 2 was the surgical control group (Y/Y group) with the isochronic parabiosis model (2-month-old/2-month-old, young/young). Group 3 consisted of the ageing control mice (2-month-old alone, Y group). Young knee cartilages collected from all three groups at 4 months after surgery were compared. Fluorescence molecular tomography (FMT) was used to confirm whether the two mice in parabiosis shared a common blood circulation at 2 weeks after surgery. The knee joints of young mice were examined radiologically at 4 months after surgery. Histological scoring was assigned to grade the severity of osteoarthritis (OA). Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were used to evaluate OA-related protein expression and gene expression, and chondrocyte proliferation was determined with EdU staining.RESULTS:FMT imaging confirmed cross-circulation in the parabiotic pairs. The percentage of EdU-positive chondrocytes in young mice from the Y/O group was significantly lower compared with those of the Y/Y and Y groups (p <0.05 for both). There was no statistically significant difference in the mRNA expression of collagen type II (Col2), collagen type X (Col10), and matrix metalloproteinase 13 (MMP13) among the three groups (P>0.05), but expression of sex-determining region Y box 9 (Sox9) mRNA in young cartilage from the Y/O group was markedly attenuated compared to those in the Y/Y and Y groups (p <0.05 for both). In the Y/O group, mRNA expression of runt-related transcription factor 2 (Runx2) in young cartilage was significantly increased compared to the Y/Y and Y groups (p <0.05 for both). The changes in Col2, Col10, MMP13, Runx2 and Sox9 at the protein level mimicked the alterations found at the mRNA level. Loss of cartilage proteoglycan in young mice from the Y/O group was significantly greater compared to the Y/Y and Y groups (p <0.05 for both), despite the lack of significant difference among the three groups in OARIS and osteophytosis scores.CONCLUSION:Heterochronic parabiosis exerts a negative effect on chondrocyte proliferation in the knee cartilage of young mice.
Highlights
Osteoarthritis (OA) is the leading cause of chronic infirmity in ageing individuals
Heterochronic parabiosis exerts a negative effect on chondrocyte proliferation in the knee cartilage of young mice
At 2 weeks after surgery, shared circulation was successfully established in the heterochronic parabiosis model, which was in line with the literature [19,20,21] and was confirmed using Fluorescence molecular tomography (FMT) examination
Summary
Ageassociated changes that affect joint tissues promote the development of OA [1, 2]. An increase in age has a greater impact on the development of primary OA than other risk factors, including obesity, genetics, sex and anatomical factors [3, 4]. Chondrocyte loss or a decline in chondrocyte proliferation has been associated with the degeneration of aged cartilage [5,6,7]. It is important to ascertain the factors that promote ageing of the cartilage with the aim to prevent or reduce cartilage dysfunction. Previous reports disclosed that heterochronic parabiosis, which refers to the parabiotic pairing of an older animal with a younger one, could in part reduce the regenerative capacity of young organs and tissues, such as the brain and muscle [8, 9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
