Stimulation of the Runx2 P1 Promoter by Collagen-derived Dipeptide Prolyl-hydroxyproline Bound to Foxg1 and Foxo1 in Osteoblasts

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2021 Nov 15

PMID 34779485

Citations 3

Authors

Kaho Nomura

Yoshifumi Kimira

Yoshihiro Osawa

Aya Kataoka-Matsushita

Koichi Takao

Yoshiaki Sugita

Jun Shimizu

Masahiro Wada

Hiroshi Mano

Affiliations

Soon will be listed here.

Abstract

Collagen-derived dipeptide prolyl-hydroxyproline (Pro-Hyp) directly binds to the forkhead box g1 (Foxg1) protein and causes it to undergo structural alteration. Pro-Hyp also promotes the production of a regulator of osteoblast differentiation, Runt-related transcription factor 2 (Runx2), through Foxg1, inducing osteoblast differentiation. In addition, Pro-Hyp disrupts the interaction between Foxg1 and Runx2, and Foxg1 appears to interact with Runx2 in the absence of Pro-Hyp. To elucidate the mechanism of Pro-Hyp that promotes osteoblast differentiation, we investigated whether Pro-Hyp regulates the Runx2 P1 promoter together with Foxg1. The present study revealed that Pro-Hyp is taken up by osteoblastic cells via the solute carrier family 15 member (Slc15a) 4. In the presence of Pro-Hyp, Runx2 is translocated from the nucleus to the cytoplasm and Foxg1 is translocated from the cytoplasm to the nucleus. We also found that Pro-Hyp promoted the interaction between Forkhead box o1 (Foxo1) and Runx2 and the dissociation of Foxg1 from Runx2. Moreover, we identified the Pro-Hyp response element in the Runx2 distal P1 promoter at nt -375 to -316, including the Runx2 binding sites and Fox core sequence. In the presence of Pro-Hyp, Runx2 is dissociated from the Pro-Hyp response element in the Runx2 distal P1 promoter. Subsequently, Foxg1 and Foxo1 activated the Runx2 promoter by binding to the Pro-Hyp response element. In summary, we delineated the mechanism by which Pro-Hyp stimulates the bone-related Runx2 distal P1 promoter activity in osteoblastic cells through Foxg1, Foxo1, and Runx2.

Citing Articles

FOXG1 interaction with SATB2 promotes autophagy to alleviate neuroinflammation and mechanical abnormal pain in rats with lumbar disc herniation.

Wang Z, Gu Y, Wang H, Chen Y, Chen H, Wang X Ann Med. 2024; 56(1):2399967.

PMID: 39624968 PMC: 11616759. DOI: 10.1080/07853890.2024.2399967.

Collagen-derived dipeptide prolyl-hydroxyproline cooperates with Foxg1 to activate the PGC-1α promoter and induce brown adipocyte-like phenotype in rosiglitazone-treated C3H10T1/2 cells.

Nomura K, Kimira Y, Kobayashi R, Shiobara Y, Osawa Y, Kataoka-Matsushita A Front Nutr. 2024; 11:1375532.

PMID: 38812940 PMC: 11133597. DOI: 10.3389/fnut.2024.1375532.

Preventive Effects of Collagen-Derived Dipeptide Prolyl-Hydroxyproline against Dexamethasone-Induced Muscle Atrophy in Mouse C2C12 Skeletal Myotubes.

Kimira Y, Osawa K, Osawa Y, Mano H Biomolecules. 2023; 13(11).

PMID: 38002299 PMC: 10669392. DOI: 10.3390/biom13111617.

References

Elam M, Johnson S, Hooshmand S, Feresin R, Payton M, Gu J . A calcium-collagen chelate dietary supplement attenuates bone loss in postmenopausal women with osteopenia: a randomized controlled trial. J Med Food. 2014; 18(3):324-31. DOI: 10.1089/jmf.2014.0100. View

Higuchi S, Sugahara F, Pascual-Anaya J, Takagi W, Oisi Y, Kuratani S . Inner ear development in cyclostomes and evolution of the vertebrate semicircular canals. Nature. 2018; 565(7739):347-350. DOI: 10.1038/s41586-018-0782-y. View

Kimira Y, Ogura K, Taniuchi Y, Kataoka A, Inoue N, Sugihara F . Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells. Biochem Biophys Res Commun. 2014; 453(3):498-501. DOI: 10.1016/j.bbrc.2014.09.121. View

Carlton A, Illendula A, Gao Y, Llaneza D, Boulton A, Shah A . Small molecule inhibition of the CBFβ/RUNX interaction decreases ovarian cancer growth and migration through alterations in genes related to epithelial-to-mesenchymal transition. Gynecol Oncol. 2018; 149(2):350-360. PMC: 5915923. DOI: 10.1016/j.ygyno.2018.03.005. View

Kumar S, Sugihara F, Suzuki K, Inoue N, Venkateswarathirukumara S . A double-blind, placebo-controlled, randomised, clinical study on the effectiveness of collagen peptide on osteoarthritis. J Sci Food Agric. 2014; 95(4):702-7. DOI: 10.1002/jsfa.6752. View

Matsuo K, Irie N . Osteoclast-osteoblast communication. Arch Biochem Biophys. 2008; 473(2):201-9. DOI: 10.1016/j.abb.2008.03.027. View

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K . Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997; 89(5):755-64. DOI: 10.1016/s0092-8674(00)80258-5. View

Xiao Z, Liu S, Hinson T, Quarles L . Characterization of the upstream mouse Cbfa1/Runx2 promoter. J Cell Biochem. 2001; 82(4):647-59. DOI: 10.1002/jcb.1192. View

Yamashita T, Shimada S, Guo W, Sato K, Kohmura E, Hayakawa T . Cloning and functional expression of a brain peptide/histidine transporter. J Biol Chem. 1997; 272(15):10205-11. DOI: 10.1074/jbc.272.15.10205. View

10.

Karsenty G . Transcriptional control of skeletogenesis. Annu Rev Genomics Hum Genet. 2008; 9:183-96. DOI: 10.1146/annurev.genom.9.081307.164437. View

11.

Gross S, Krause Y, Wuelling M, Vortkamp A . Hoxa11 and Hoxd11 regulate chondrocyte differentiation upstream of Runx2 and Shox2 in mice. PLoS One. 2012; 7(8):e43553. PMC: 3423364. DOI: 10.1371/journal.pone.0043553. View

12.

Genin E, Caron N, Vandenbosch R, Nguyen L, Malgrange B . Concise review: forkhead pathway in the control of adult neurogenesis. Stem Cells. 2014; 32(6):1398-407. DOI: 10.1002/stem.1673. View

13.

Pal S, Maurya S, Chattopadhyay S, Pal China S, Porwal K, Kulkarni C . The osteogenic effect of liraglutide involves enhanced mitochondrial biogenesis in osteoblasts. Biochem Pharmacol. 2019; 164:34-44. PMC: 7234838. DOI: 10.1016/j.bcp.2019.03.024. View

14.

Kimira Y, Odaira H, Nomura K, Taniuchi Y, Inoue N, Nakatani S . Collagen-derived dipeptide prolyl-hydroxyproline promotes osteogenic differentiation through Foxg1. Cell Mol Biol Lett. 2017; 22:27. PMC: 5710072. DOI: 10.1186/s11658-017-0060-2. View

15.

Otto F, Thornell A, Crompton T, Denzel A, Gilmour K, Rosewell I . Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 1997; 89(5):765-71. DOI: 10.1016/s0092-8674(00)80259-7. View

16.

Liu J, Zhang B, Song S, Ma M, Si S, Wang Y . Bovine collagen peptides compounds promote the proliferation and differentiation of MC3T3-E1 pre-osteoblasts. PLoS One. 2014; 9(6):e99920. PMC: 4057461. DOI: 10.1371/journal.pone.0099920. View

17.

Ducy P, Zhang R, Geoffroy V, Ridall A, Karsenty G . Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89(5):747-54. DOI: 10.1016/s0092-8674(00)80257-3. View

18.

Iyer S, Ambrogini E, Bartell S, Han L, Roberson P, de Cabo R . FOXOs attenuate bone formation by suppressing Wnt signaling. J Clin Invest. 2013; 123(8):3409-19. PMC: 3726166. DOI: 10.1172/JCI68049. View

19.

Harrington K, Javed A, Drissi H, McNeil S, Lian J, Stein J . Transcription factors RUNX1/AML1 and RUNX2/Cbfa1 dynamically associate with stationary subnuclear domains. J Cell Sci. 2002; 115(Pt 21):4167-76. DOI: 10.1242/jcs.00095. View

20.

Drissi H, Luc Q, Shakoori R, Chuva De Sousa Lopes S, Choi J, Terry A . Transcriptional autoregulation of the bone related CBFA1/RUNX2 gene. J Cell Physiol. 2000; 184(3):341-50. DOI: 10.1002/1097-4652(200009)184:3<341::AID-JCP8>3.0.CO;2-Z. View