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Dergiler / Trakya University Journal of Natural Sciences / 2026 / Volume: 27 Issue: 1

Interaction between circadian gene Bmal1 and adipogenic regulator PPARγ in UVB-exposed mesenchymal stem cells

Afra Keban(HACETTEPE UNIVERSITY, FACULTY OF SCIENCE, DEPARTMENT OF BIOLOGY, BIOLOGY PR.)0009-0000-1379-0759
Elçin Tank(HACETTEPE UNIVERSITY, FACULTY OF SCIENCE, DEPARTMENT OF BIOLOGY, BIOLOGY PR.)0009-0006-1346-4965
Beril Erdem Tunçdemir(HACETTEPE UNIVERSITY, FACULTY OF SCIENCE, DEPARTMENT OF BIOLOGY, BIOLOGY PR.)0000-0002-9820-1147
Esin Akbay Çetin(HACETTEPE UNIVERSITY, FACULTY OF SCIENCE, DEPARTMENT OF BIOLOGY, BIOLOGY PR.)0000-0002-0797-8322
Sayfa
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Yayın Tarihi
2026-07-09
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Moreover, adipogenic differentiation itself appears to contribute to the regulation of the circadian rhythm.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Background: Mesenchymal stem cells (MSCs), including adipose-derived MSCs (ADMSCs) and bone marrow-derived MSCs (BMMSCs), are multipotent cells essential for tissue repair, with strong self-renewal and differentiation abilities.
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Temel Bulgular & Veri:Bmal1 is a core component of the circadian cycle and plays a regulatory role in stem cell specialization; PPARγ links adipogenesis to the circadian rhythm by epigenetically regulating Bmal1.
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Sonuç & Katkı:Moreover, adipogenic differentiation itself appears to contribute to the regulation of the circadian rhythm.
🔬Tür:Research Article
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Mesenchymal stem cell · Bmal1 · PPARγ

Abstract

Background: Mesenchymal stem cells (MSCs), including adipose-derived MSCs (ADMSCs) and bone marrow-derived MSCs (BMMSCs), are multipotent cells essential for tissue repair, with strong self-renewal and differentiation abilities. Bmal1 is a core component of the circadian cycle and plays a regulatory role in stem cell specialization; PPARγ links adipogenesis to the circadian rhythm by epigenetically regulating Bmal1. Ultraviolet B (UVB) radiation influences circadian processes by modulating the expression of growth factors and cytokines in MSCs. Aims: This study investigated how UVB affects adipogenesis and circadian-system-related gene transcription in ADMSCs and BMMSCs. Methods: MSC viability post-exposure was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis. Cells were cultured in adipogenesis medium and stained with Oil Red O at multiple time points. UVB-treated MSCs were maintained under differentiation-inducing conditions for 28 days, and gene expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Viability assays identified 25 mJ/cm² as the optimal UVB dose. Flow cytometry confirmed the enhanced expression of MSC markers (CD54, CD90, and CD29) and low expression of hematopoietic markers (CD45, CD106, and MHC class II). Oil Red O staining revealed gradual lipid accumulation, beginning on day 14 and forming mature droplets by day 28. qRT-PCR indicated a significant increase in PPARγ expression in adipogenic differentiation groups and Bmal1 expression post-UVB exposure. Conclusion: Overall, these findings suggest that UVB stimulation at optimal doses enhances the adipogenic differentiation capacity of MSCs while modulating circadian rhythm-associated genes. Moreover, adipogenic differentiation itself appears to contribute to the regulation of the circadian rhythm.

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Bu Makaleye Atıf Yap

Keban, A., Tank, E., Tunçdemir, B. E., Çetin, E. A. (2026). Interaction between circadian gene Bmal1 and adipogenic regulator PPARγ in UVB-exposed mesenchymal stem cells. Trakya University Journal of Natural Sciences, Volume: 27 Issue: 1. https://doi.org/10.23902/trkjnat.2025121

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Kaynakça (51)

  1. Andersen, B., Duan, J., & Karri, S. S. (2023). How and why the circadian clock regulates proliferation of adult epithelial stem cells. Stem Cells, 41(4), 319–327. https://doi.org/10.1093/stmcls/sxad013
  2. Angelina, J., Putra, A., Trisnadi, S., Hermansyah, D., Setiawan, E., Sumarawati, T., & Amalina, N. D. (2025). Hypoxia-conditioned mesenchymal stem cells (MSC) exosomes attenuate ultraviolet-B (UVB)-mediated malondialdehyde (MDA) and matrix metalloproteinase-1 (MMP-1) upregulation in collagen loss models. Medicinski Glasnik, 22(1). https://doi.org/10.17392/1923-22-01
  3. Ansarin, A., Mahdavi, A. M., Javadivala, Z., Shanehbandi, D., Zarredar, H., & Ansarin, K. (2023). The cross-talk between leptin and circadian rhythm signaling proteins in physiological processes: A systematic review. Molecular Biology Reports, 50(12), 10427–10443. https://doi.org/10.1007/s11033-023- 08887-3
  4. Boucher, H., Vanneaux, V., Domet, T., Parouchev, A., & Larghero, J. (2016). Circadian clock genes modulate human bone marrow mesenchymal stem cell differentiation, migration and cell cycle. PLOS ONE, 11(1), e0146674. https:// doi.org/10.1371/journal.pone.0146674
  5. Carvalho, C., Silva, R., Melo, T. M. V. D. P. e, Inga, A., & Saraiva, L. (2024). P53 and the ultraviolet radiation-induced skin response: Finding the light in the darkness of triggered carcinogenesis. Cancers, 16(23), 3978. https://doi. org/10.3390/cancers16233978
  6. Česnik, A. B., & Švajger, U. (2024). The issue of heterogeneity of MSC-based advanced therapy medicinal products-a review. Frontiers in Cell and Developmental Biology, 12, 1400347. https://doi.org/10.3389/fcell.2024.1400347
  7. Christoffers, S., Seiler, L., Wiebe, E., & Blume, C. (2024). Possibilities and efficiency of MSC co-transfection for gene therapy. Stem Cell Research & Therapy, 15(1), 150. https://doi.org/10.1186/s13287-024-03757-6
  8. Civelek, E., Ozturk Civelek, D., Akyel, Y. K., Kaleli Durman, D., & Okyar, A. (2023). Circadian dysfunction in adipose tissue: Chronotherapy in metabolic diseases. Biology, 12(8), 1077. https://doi.org/10.3390/biology12081077
  9. Çetin, E. A., Babayiğit, E. H., Özdemir, A. Y., Erfen, Ş., & Onur, M. A. (2023). Investigation of UV-treated mesenchymal stem cells in an in vitro wound model. In Vitro Cellular & Developmental Biology-Animal, 59(5), 331–345. https://doi. org/10.1007/s11626-023-00772-4
  10. El-Badawy, A., Amer, M., Abdelbaset, R., Sherif, S. N., Abo-Elela, M., Ghallab, Y. H., Abdelhamid, H., Ismail, Y., & El-Badri, N. (2016). Adipose stem cells display higher regenerative capacities and more adaptable electro-kinetic properties compared to bone marrow-derived mesenchymal stromal cells. Scientific Reports, 6, 37801. https://doi.org/10.1038/srep37801
  11. Erickson, M. L., Dobias, D., Keleher, M. R., Dabelea, D., Bergman, B. C., Broussard, J. L., & Boyle, K. E. (2024). In vitro circadian clock gene expression assessments in mesenchymal stem cells from human infants: A pilot study. Nutrients, 16(1), 52. https://doi.org/10.3390/nu16010052
  12. Ezati, P., Khan, A., Priyadarshi, R., Bhattacharya, T., Tammina, S. K., & Rhim, J.-W. (2023). Biopolymer-based UV protection functional films for food packaging. Food Hydrocolloids, 142, 108771. https://doi.org/10.1016/j. foodhyd.2023.108771
  13. Gao, W., Li, R., Ye, M., Zhang, L., Zheng, J., Yang, Y., Wei, X., & Zhao, Q. (2022). The circadian clock has roles in mesenchymal stem cell fate decision. Stem Cell Research & Therapy, 13(1), 200. https://doi.org/10.1186/s13287-022- 02878-0
  14. Goodenow, D., Greer, A. J., Cone, S. J., & Gaddameedhi, S. (2022). Circadian effects on UV-induced damage and mutations. Mutation Research - Reviews in Mutation Research, 789, 108413. https://doi.org/10.1016/j. mrrev.2022.108413
  15. Göncü, B., & Öztürk, D. (2019). HT29 hücre hattında sirkadiyen ritme bağlı gen ifadesinin kontrolünde referans gen farklılığının senkronizasyondaki rolü. Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 12(3), 1370–1380. https:// doi.org/10.18185/erzifbed.523088
  16. Grimaldi, B., Bellet, M. M., Katada, S., Astarita, G., Hirayama, J., Amin, R. H., Granneman, J. G., Piomelli, D., Leff, T., & Sassone-Corsi, P. (2010). PER2 controls lipid metabolism by direct regulation of PPARγ. Cell Metabolism, 12(5), 509–520. https://doi.org/10.1016/j.cmet.2010.10.005
  17. Guillamat-Prats, R. (2021). The role of MSC in wound healing, scarring, and regeneration. Cells, 10(7), 1729.
  18. Kaneko, H., Kaitsuka, T., & Tomizawa, K. (2023). Artificial induction of circadian rhythm by combining exogenous BMAL1 expression and polycomb repressive complex 2 inhibition in human induced pluripotent stem cells. Cellular and Molecular Life Sciences, 80(8), 200. https://doi.org/10.1007/s00018-023- 04847-z
  19. Lamnis, L., Christofi, C., Stark, A., Palm, H., Roemer, K., Vogt, T., & Reichrath, J. (2024). Differential regulation of circadian clock genes by UV-B radiation and 1,25-dihydroxyvitamin D: A pilot study during different stages of skin photocarcinogenesis. Nutrients, 16(2), 254. https://doi.org/10.3390/nu16020254
  20. Li, W., Wang, Y., Liu, C., Yu, Y., Xu, L., & Dong, B. (2025). Evaluation of the regulatory effect of the pan-PPAR agonist chiglitazar on the dawn phenomenon. Diabetes Therapy, 16(4), 731–748. https://doi.org/10.1007/ s13300-025-01708-9
  21. Li, Z., Li, Y., Xu, X., Gu, J., Chen, H., & Gui, Y. (2023a). Exosomes rich in Wnt5 improved circadian rhythm dysfunction via enhanced PPARγ activity in the 6-hydroxydopamine model of Parkinson’s disease. Neuroscience Letters, 802, 137139. https://doi.org/10.1016/j.neulet.2023.137139
  22. Li, Z., Yan, T., & Fang, X. (2023b). Low-dimensional wide-bandgap semiconductors for UV photodetectors. Nature Reviews Materials, 8, 587–603. https://doi.org/10.1038/s41578-023-00583-9
  23. Liao, W., Duan, X., Xie, F., Zheng, D., Yang, P., Wang, X., & Hu, Z. (2023). 3D-bioprinted double-crosslinked angiogenic alginate/chondroitin sulfate patch for diabetic wound healing. International Journal of Biological Macromolecules, 236, 123952. https://doi.org/10.1016/j.ijbiomac.2023.123952
  24. Lotfy, A., AboQuella, N. M., & Wang, H. (2023). Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials. Stem Cell Research & Therapy, 14(1), 66. https://doi.org/10.1186/s13287-023-03287-7
  25. Lotfy, A., El-Sherbiny, Y. M., Cuthbert, R., Jones, E., & Badawy, A. M. (2019). Comparative study of biological characteristics of mesenchymal stem cells isolated from mouse bone marrow and peripheral blood. Biomedical Reports, 11, 165–170. https://doi.org/10.3892/br.2019.1236
  26. Mattis, J., & Sehgal, A. (2016). Circadian rhythms, sleep, and disorders of aging. Trends in Endocrinology & Metabolism, 27(4), 192–203. https://doi. org/10.1016/j.tem.2016.02.003
  27. Mens, M. M. J., & Ghanbari, M. (2018). Cell cycle regulation of stem cells by microRNAs. Stem Cell Reviews and Reports, 14, 309–322. https://doi. org/10.1007/s12015-018-9808-y
  28. Mohamed-Ahmed, S., Fristad, I., Lie, S. A., Suliman, S., Mustafa, K., Vindenes, H., & Idris, S. B. (2018). Adipose-derived and bone marrow mesenchymal stem cells: A donor-matched comparison. Stem Cell Research & Therapy, 9(1), 168. https://doi.org/10.1186/s13287-018-0914-1
  29. Montaigne, D., Butruille, L., & Staels, B. (2021). PPAR control of metabolism and cardiovascular functions. Nature Reviews Cardiology, 18(12), 809–823. https://doi.org/10.1038/s41569-021-00569-6
  30. Ninomiya, Y., Sugahara-Yamashita, Y., Nakachi, Y., Tokuzawa, Y., Okazaki, Y., & Nishiyama, M. (2010). Development of a rapid culture method to induce adipocyte differentiation of human bone marrow-derived mesenchymal stem cells. Biochemical and Biophysical Research Communications, 394(2), 303–308. https://doi.org/10.1016/j.bbrc.2010.03.001
  31. Niyaz, M., Gürpınar, Ö. A., Günaydın, S., & Onur, M. A. (2012). Isolation, culturing and characterization of rat adipose tissue-derived mesenchymal stem cells: A simple technique. Turkish Journal of Biology, 36(6), 658–664. https:// doi.org/10.3906/biy-1109-31
  32. Perez, R. L., Brauer, J., Rühle, A., Trinh, T., Sisombath, S., Wuchter, P., Grosu, A. L., Debus, J., Saffrich, R., Huber, P. E., & Nicolay, N. H. (2019). Human mesenchymal stem cells are resistant to UV-B irradiation. Scientific Reports, 9(1), 20000. https://doi.org/10.1038/s41598-019-56591-9
  33. Pittenger, M. F., Discher, D. E., Péault, B. M., Phinney, D. G., Hare, J. M., & Caplan, A. I. (2019). Mesenchymal stem cell perspective: Cell biology to clinical progress. NPJ Regenerative Medicine, 4, 22. https://doi.org/10.1038/s41536-019- 0083-6
  34. Putthanbut, N., Su, P. A. B., Lee, J. Y., & Borlongan, C. V. (2025). Circadian rhythms in stem cells and their therapeutic potential. Stem Cell Research & Therapy, 16(1), 85. https://doi.org/10.1186/s13287-025-04178-9
  35. Ra, K., Park, S. C., & Lee, B. C. (2023). Female reproductive aging and oxidative stress: Mesenchymal stem cell conditioned medium as a promising antioxidant. International Journal of Molecular Sciences, 24(5), 5053. https:// doi.org/10.3390/ijms24055053
  36. Sani, M. A., Khezerlou, A., Tavassoli, M., Abedini, A. H., & McClements, D. J. (2024). Development of sustainable UV-screening food packaging materials: A review of recent advances. Trends in Food Science & Technology, 145, 104366. https://doi.org/10.1016/j.tifs.2024.104366
  37. Sevim, H., Kocaefe, Y. Ç., Onur, M. A., Uçkan-Çetinkaya, D., & Gürpınar, Ö. A. (2018). Bone marrow derived mesenchymal stem cells ameliorate inflammatory response in an in vitro model of familial hemophagocytic lymphohistiocytosis 2. Stem Cell Research & Therapy, 9(1), 198. https://doi.org/10.1186/s13287-018- 0941-y
  38. Su, Z., Hu, Q., Li, X., Wang, Z., & Xie, Y. (2024). The influence of circadian rhythms on DNA damage repair in skin photoaging. International Journal of Molecular Sciences, 25(20), 10926. https://doi.org/10.3390/ijms252010926
  39. Takahashi, J. S. (2017). Transcriptional architecture of the mammalian circadian clock. Nature Reviews Genetics, 18(3), 164–179. https://doi.org/10.1038/ nrg.2016.150
  40. Tian, Y., Luan, X., & Yang, K. (2024). Chronotherapy involving rosiglitazone regulates the phenotypic switch of vascular smooth muscle cells by shifting the phase of TNF-α rhythm through triglyceride accumulation in macrophages. Heliyon, 10(10), e30708. https://doi.org/10.1016/j.heliyon.2024.e30708
  41. Vilar, A., Hodgson-Garms, M., & Frith, J. E. (2023). Substrate mechanical properties bias MSC paracrine activity and therapeutic potential. Acta Biomaterialia, 168, 1–15. https://doi.org/10.1016/j.actbio.2023.06.041
  42. Wang, S., Lin, Y., Gao, L., Yang, Z., Lin, J., Ren, S., Li, F., Chen, J., Wang, Z., Dong, Z., Sun, P., & Wu, B. (2022). PPAR-γ integrates obesity and adipocyte clock through epigenetic regulation of Bmal1. Theranostics, 12(4), 1589–1606. https://doi.org/10.7150/thno.69054
  43. Wong, D. Y., Ranganath, T., & Kasko, A. M. (2015). Low-dose, long-wave UV light does not affect gene expression of human mesenchymal stem cells. PLOS ONE, 10(9), e0139307. https://doi.org/10.1371/journal.pone.0139307
  44. Xiong, X., Kiperman, T., Li, W., Dhawan, S., Lee, J., Yechoor, V., & Ma, K. (2023). The clock-modulatory activity of nobiletin suppresses adipogenesis via Wnt signaling. Endocrinology, 164(8), bqad096. https://doi.org/10.1210/endocr/ bqad096
  45. Yan, T., Huang, L., Yan, Y., Zhong, Y., Xie, H., & Wang, X. (2023). MAPK/ AP-1 signaling pathway is involved in the protection mechanism of bone marrow mesenchymal stem cells-derived exosomes against ultraviolet-induced photoaging in human dermal fibroblasts. Skin Pharmacology and Physiology, 36(2), 98–106. https://doi.org/10.1159/000529551
  46. Yin, X., Lin, L., Fang, F., Zhang, B., & Shen, C. (2023). Mechanisms and optimization strategies of paracrine exosomes from mesenchymal stem cells in ischemic heart disease. Stem Cells International, 2023, 6500831. https://doi. org/10.1155/2023/6500831
  47. Zeng, Y., Guo, Z., Wu, M., Chen, F., & Chen, L. (2024). Circadian rhythm regulates the function of immune cells and participates in the development of tumors. Cell Death Discovery, 10(1), 199. https://doi.org/10.1038/s41420-024- 01960-1
  48. Zhang, L., Zhang, C., Zheng, J., Wang, Y., Wei, X., Yang, Y., & Zhao, Q. (2024). miR-155-5p/Bmal1 modulates the senescence and osteogenic differentiation of mouse BMSCs through the Hippo signaling pathway. Stem Cell Reviews and Reports, 20(2), 554–567. https://doi.org/10.1007/s12015-023-10666-3
  49. Zhang, Y., Li, Y., Gao, N., Gong, Y., Shi, W., & Wang, X. (2023). Transcriptome and metabolome analyses reveal perfluorooctanoic acid-induced kidney injury by interfering with PPAR signaling pathway. International Journal of Molecular Sciences, 24(14), 11503. https://doi.org/10.3390/ijms241411503
  50. Zhu, Y., Liu, T., Song, K., Fan, X., Ma, X., & Cui, Z. (2008). Adipose-derived stem cell: A better stem cell than BMSC. Cell Biochemistry and Function, 26(6), 664–675. https://doi.org/10.1002/cbf.1488
  51. Zhu, Z., Guo, L., Yeltai, N., Xu, H., & Zhang, Y. (2022). Chemokine (C-C motif) ligand 2-enhanced adipogenesis and angiogenesis of human adipose-derived stem cell and human umbilical vein endothelial cell co-culture system in adipose tissue engineering. Journal of Tissue Engineering and Regenerative Medicine, 16(2), 163–176. https://doi.org/10.1002/term.3264 Zou, X., Zou, D., Li, L., Yu, R., Li, X., Du, X., Guo, J., Wang, K., & Liu, W. (2022). Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium. Stem Cell Research & Therapy, 13, 435. https://doi.org/10.1186/s13287-022-03137-y