HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway
The association of tendinopathy with diabetes has been well recognized. Tendon stem/progenitor cells (TSPCs) play critical roles in tendon repair, regeneration, and homeostasis maintenance. Diabetic TSPCs exhibit enhanced erroneous differentiation and are involved in the pathogenesis of diabetic ten...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2024-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2024/2335270 |
| _version_ | 1797203741597761536 |
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| author | Panpan Lu Guangchun Dai Liu Shi Yingjuan Li Ming Zhang Hao Wang Yunfeng Rui |
| author_facet | Panpan Lu Guangchun Dai Liu Shi Yingjuan Li Ming Zhang Hao Wang Yunfeng Rui |
| author_sort | Panpan Lu |
| collection | DOAJ |
| description | The association of tendinopathy with diabetes has been well recognized. Tendon stem/progenitor cells (TSPCs) play critical roles in tendon repair, regeneration, and homeostasis maintenance. Diabetic TSPCs exhibit enhanced erroneous differentiation and are involved in the pathogenesis of diabetic tendinopathy, whereas the underlying mechanism of the erroneous differentiation of TSPCs remains unclear. Here, we showed that high glucose treatment promoted the erroneous differentiation of TSPCs with increased osteogenic differentiation capacity and decreased tenogenic differentiation ability, and stimulated the expression and further secretion of HMGB1 in TSPCs and. Functionally, exogenous HMGB1 significantly enhanced the erroneous differentiation of TSPCs, while HMGB1 knockdown mitigated high glucose-promoted erroneous differentiation of TSPCs. Mechanistically, the RAGE/β-catenin signaling was activated in TSPCs under high glucose, and HMGB1 knockdown inhibited the activity of RAGE/β-catenin signaling. Inhibition of RAGE/β-catenin signaling could ameliorate high glucose-induced erroneous differentiation of TSPCs. These results indicated that HMGB1 regulated high glucose-induced erroneous differentiation of TSPCs through the RAGE/β-catenin signaling pathway. Collectively, our findings suggest a novel essential mechanism of the erroneous differentiation of TSPCs, which might contribute to the pathogenesis of diabetic tendinopathy and provide a promising therapeutic target and approach for diabetic tendinopathy. |
| first_indexed | 2024-04-24T08:24:09Z |
| format | Article |
| id | doaj.art-de65a25dadbd4fc7ad93a7d3e4b7fabc |
| institution | Directory Open Access Journal |
| issn | 1687-9678 |
| language | English |
| last_indexed | 2024-04-24T08:24:09Z |
| publishDate | 2024-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj.art-de65a25dadbd4fc7ad93a7d3e4b7fabc2024-04-17T00:00:02ZengHindawi LimitedStem Cells International1687-96782024-01-01202410.1155/2024/2335270HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin PathwayPanpan Lu0Guangchun Dai1Liu Shi2Yingjuan Li3Ming Zhang4Hao Wang5Yunfeng Rui6Department of OrthopaedicsDepartment of OrthopaedicsDepartment of OrthopaedicsSchool of MedicineDepartment of OrthopaedicsDepartment of OrthopaedicsDepartment of OrthopaedicsThe association of tendinopathy with diabetes has been well recognized. Tendon stem/progenitor cells (TSPCs) play critical roles in tendon repair, regeneration, and homeostasis maintenance. Diabetic TSPCs exhibit enhanced erroneous differentiation and are involved in the pathogenesis of diabetic tendinopathy, whereas the underlying mechanism of the erroneous differentiation of TSPCs remains unclear. Here, we showed that high glucose treatment promoted the erroneous differentiation of TSPCs with increased osteogenic differentiation capacity and decreased tenogenic differentiation ability, and stimulated the expression and further secretion of HMGB1 in TSPCs and. Functionally, exogenous HMGB1 significantly enhanced the erroneous differentiation of TSPCs, while HMGB1 knockdown mitigated high glucose-promoted erroneous differentiation of TSPCs. Mechanistically, the RAGE/β-catenin signaling was activated in TSPCs under high glucose, and HMGB1 knockdown inhibited the activity of RAGE/β-catenin signaling. Inhibition of RAGE/β-catenin signaling could ameliorate high glucose-induced erroneous differentiation of TSPCs. These results indicated that HMGB1 regulated high glucose-induced erroneous differentiation of TSPCs through the RAGE/β-catenin signaling pathway. Collectively, our findings suggest a novel essential mechanism of the erroneous differentiation of TSPCs, which might contribute to the pathogenesis of diabetic tendinopathy and provide a promising therapeutic target and approach for diabetic tendinopathy.http://dx.doi.org/10.1155/2024/2335270 |
| spellingShingle | Panpan Lu Guangchun Dai Liu Shi Yingjuan Li Ming Zhang Hao Wang Yunfeng Rui HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway Stem Cells International |
| title | HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway |
| title_full | HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway |
| title_fullStr | HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway |
| title_full_unstemmed | HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway |
| title_short | HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/β-Catenin Pathway |
| title_sort | hmgb1 modulates high glucose induced erroneous differentiation of tendon stem progenitor cells through rage β catenin pathway |
| url | http://dx.doi.org/10.1155/2024/2335270 |
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