DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence
Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)–SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Journal of Orthopaedic Translation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X23000554 |
| _version_ | 1797706843691155456 |
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| author | Yuan-Chao Sun Pei-Hung Shen Chih-Chien Wang Hsin-Ya Liu Chieh-Hua Lu Sheng-Chiang Su Jhih-Syuan Liu Peng-Fei Li Chia-Luen Huang Li-Ju Ho Yi-Jen Hung Chien-Hsing Lee Feng-Chih Kuo |
| author_facet | Yuan-Chao Sun Pei-Hung Shen Chih-Chien Wang Hsin-Ya Liu Chieh-Hua Lu Sheng-Chiang Su Jhih-Syuan Liu Peng-Fei Li Chia-Luen Huang Li-Ju Ho Yi-Jen Hung Chien-Hsing Lee Feng-Chih Kuo |
| author_sort | Yuan-Chao Sun |
| collection | DOAJ |
| description | Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)–SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed to examine the influence of age and body mass index (BMI) on the features of IFPs and IFP-derived cells (IFP–SCs and IFP-DFATs) with exploration of the clinical utilization of IFP-DFATs. Methods: We collected IFPs with isolation of paired IFP-SCs and IFP-DFATs from individuals aged 65 years and older with distinct body weights who underwent total knee replacement for osteoarthritis (OA). Flow cytometry was used to characterize the cellular immunophenotypes. Adipogenesis and chondrogenesis were performed in vitro. Real-time qPCR, western blotting, and Oil Red O or Alcian blue staining were performed to evaluate inflammation, adipogenesis, and chondrogenesis. RNA sequencing and Seahorse analyses were conducted to explore the underlying mechanisms. Results: We found that IFPs from old or normal-weight individuals with knee OA were pro-inflammatory, and that interleukin-6 (IL-6) signaling was associated with multiple immune-related molecules, whereas IFP-derived cells could escape the inflammatory properties. Aging plays an important role in diminishing the chondrogenic and adipogenic abilities of IFP-SCs; however, this effect was avoided in IFP-DFATs. Generally, IFP-DFATs presented a steady state of chondrogenesis (less influenced by age) and consistently enhanced adipogenesis compared to paired IFP-SCs in different age or BMI groups. RNA sequencing and Seahorse analysis suggested that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function may contribute to the improved cellular biology of IFP-DFATs. Conclusions: Our data indicate that IFP-DFATs are superior cell material compared to IFP-SCs for cartilage differentiation and adipogenesis, particularly in advanced aging patients with knee OA. The translational potential of this article: These results provide a novel concept and supportive evidence for the use of IFP-DFATs for cell therapy or tissue engineering in patients with knee OA. Using Ingenuity Pathway Analysis (IPA) of RNA-seq data and Seahorse analysis of mitochondrial metabolic parameters, we highlighted that some molecules, signaling pathways, and mitochondrial functions are likely to be jointly coordinated to determine the enhanced biological function in IFP-DFATs. |
| first_indexed | 2024-03-12T05:58:23Z |
| format | Article |
| id | doaj.art-3d0b6f043c024a0b8bf4a4622d87ad2e |
| institution | Directory Open Access Journal |
| issn | 2214-031X |
| language | English |
| last_indexed | 2024-03-12T05:58:23Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj.art-3d0b6f043c024a0b8bf4a4622d87ad2e2023-09-03T04:23:54ZengElsevierJournal of Orthopaedic Translation2214-031X2023-09-0142113126DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influenceYuan-Chao Sun0Pei-Hung Shen1Chih-Chien Wang2Hsin-Ya Liu3Chieh-Hua Lu4Sheng-Chiang Su5Jhih-Syuan Liu6Peng-Fei Li7Chia-Luen Huang8Li-Ju Ho9Yi-Jen Hung10Chien-Hsing Lee11Feng-Chih Kuo12Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, TaiwanDepartment of Orthopedics, Tri-Service General Hospital and National Defense Medical Center, Taipei, TaiwanDepartment of Orthopedics, Tri-Service General Hospital and National Defense Medical Center, Taipei, TaiwanBeYoung Research Institute, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Corresponding author.Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan; Corresponding author. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Corresponding author. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)–SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed to examine the influence of age and body mass index (BMI) on the features of IFPs and IFP-derived cells (IFP–SCs and IFP-DFATs) with exploration of the clinical utilization of IFP-DFATs. Methods: We collected IFPs with isolation of paired IFP-SCs and IFP-DFATs from individuals aged 65 years and older with distinct body weights who underwent total knee replacement for osteoarthritis (OA). Flow cytometry was used to characterize the cellular immunophenotypes. Adipogenesis and chondrogenesis were performed in vitro. Real-time qPCR, western blotting, and Oil Red O or Alcian blue staining were performed to evaluate inflammation, adipogenesis, and chondrogenesis. RNA sequencing and Seahorse analyses were conducted to explore the underlying mechanisms. Results: We found that IFPs from old or normal-weight individuals with knee OA were pro-inflammatory, and that interleukin-6 (IL-6) signaling was associated with multiple immune-related molecules, whereas IFP-derived cells could escape the inflammatory properties. Aging plays an important role in diminishing the chondrogenic and adipogenic abilities of IFP-SCs; however, this effect was avoided in IFP-DFATs. Generally, IFP-DFATs presented a steady state of chondrogenesis (less influenced by age) and consistently enhanced adipogenesis compared to paired IFP-SCs in different age or BMI groups. RNA sequencing and Seahorse analysis suggested that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function may contribute to the improved cellular biology of IFP-DFATs. Conclusions: Our data indicate that IFP-DFATs are superior cell material compared to IFP-SCs for cartilage differentiation and adipogenesis, particularly in advanced aging patients with knee OA. The translational potential of this article: These results provide a novel concept and supportive evidence for the use of IFP-DFATs for cell therapy or tissue engineering in patients with knee OA. Using Ingenuity Pathway Analysis (IPA) of RNA-seq data and Seahorse analysis of mitochondrial metabolic parameters, we highlighted that some molecules, signaling pathways, and mitochondrial functions are likely to be jointly coordinated to determine the enhanced biological function in IFP-DFATs.http://www.sciencedirect.com/science/article/pii/S2214031X23000554AgeAdipogenesisChondrogenesisDedifferentiated fat cellsInfrapatellar fat padKnee osteoarthritis |
| spellingShingle | Yuan-Chao Sun Pei-Hung Shen Chih-Chien Wang Hsin-Ya Liu Chieh-Hua Lu Sheng-Chiang Su Jhih-Syuan Liu Peng-Fei Li Chia-Luen Huang Li-Ju Ho Yi-Jen Hung Chien-Hsing Lee Feng-Chih Kuo DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence Journal of Orthopaedic Translation Age Adipogenesis Chondrogenesis Dedifferentiated fat cells Infrapatellar fat pad Knee osteoarthritis |
| title | DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence |
| title_full | DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence |
| title_fullStr | DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence |
| title_full_unstemmed | DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence |
| title_short | DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence |
| title_sort | dfats derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence |
| topic | Age Adipogenesis Chondrogenesis Dedifferentiated fat cells Infrapatellar fat pad Knee osteoarthritis |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X23000554 |
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