GDNF secreted by pre-osteoclasts induces migration of bone marrow mesenchymal stem cells and stimulates osteogenesis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrowderived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.
Abstract
Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrowderived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.
참고문헌 (34)
- Frost HM, "Tetracycline-based histological analysis of bone remodeling", Calcif Tissue Res, 3, pp.211~237 (1969)
- Eriksen EF, "Cellular mechanisms of bone remodeling", Rev Endocr Metab Disord, 11, pp.219~227 (2010)
- Parfitt AM, "The coupling of bone formation to bone resorption : a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosis", Metab Bone Dis Relat Res, 4, pp.1~6 (1982)
- Martin TJ, "Osteoclast-derived activity in the coupling of bone formation to resorption", Trends Mol Med, 11, pp.76~81 (2005)
- Kyoji Ikeda, "Factors and Mechanisms Involved in the Coupling from Bone Resorption to Formation: How Osteoclasts Talk to Osteoblasts", 대한골대사학회지, 21(3), pp.163~167 (2014), 대한골대사학회
- Han Y, "Paracrine and endocrine actions of bone – the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts", Bone Res, 6, pp.1~11 (2018)
- Tang Y, "TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formation", Nat Med, 15, pp.757~765 (2009)
- Woo J-T, "Receptor activator of NF-κB ligand induces the fusion of mononuclear preosteoclasts into multinucleated osteoclasts", Cytotechnology, 33, pp.203~211 (2000)
- Xie H, "PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis", Nat Med, 20, pp.1270~1278 (2014)
- Su P, "Mesenchymal stem cell migration during bone formation and bone diseases therapy", Int J Mol Sci, 19, pp.2343~ (2018)
- Saarma M, "GDNF – a stranger in the TGF-β superfamily?", Eur J Biochem, 267, pp.6968~6971 (2000)
- Airaksinen MS, "GDNF family neurotrophic factor signaling: four masters, one servant?", Mol Cell Neurosci, 13, pp.313~325 (1999)
- Airaksinen MS, "The GDNF family : signalling, biological functions and therapeutic value", Nature Rev Neurosci, 3, pp.383~394 (2002)
- Amoresano A, "Direct interactions among Ret, GDNF and GFR1 molecules reveal new insights into the assembly of a functional three-protein complex", Cell Signal, 17, pp.717~727 (2005)
- Alao JP, "Selective inhibition of RET mediated cell proliferation in vitro by the kinase inhibitor SPP86", BMC Cancer, 14, pp.853~ (2014)
- Castellano E, "RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression", Nat Commun, 7, pp.1~13 (2016)
- Crupi MJ, "GGA3-mediated recycling of the RET receptor tyrosine kinase contributes to cell migration and invasion", Oncogene, 39, pp.1361~1377 (2019)
- Rangasamy SB, "Neurotrophic factor therapy for Parkinson’s disease;in Progress in brain research", pp.237~264 (2010), Elsevier
- Yang M, "Osteoclast stimulatory transmembrane protein(OC-STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation", J Cell Physiol, 215, pp.497~505 (2008)
- Xian L, "Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells", Nat Med, 18, pp.1095~ (2012)
- Yamamoto Y, "Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-κB ligand", Endocrinology, 147, pp.3366~3374 (2006)
- T. John Martin, "Bone Biology and Anabolic Therapies for Bone: Current Status and Future Prospects", 대한골대사학회지, 21(1), pp.8~20 (2014), 대한골대사학회
- Kreja, L., "Nonresorbing osteoclasts induce migration and osteogenic differentiation of mesenchymal stem cells", J Cell Biochem, 109, pp.347~355 (2010)
- 김인영, "The IRF2BP2-KLF2 axis regulates osteoclast and osteoblast differentiation", BMB Reports, 52(7), pp.469~474 (2019), 생화학분자생물학회[DOI]
- Yuli Wang, "Human amnion-derived mesenchymal stem cells induced osteogenesis and angiogenesis in human adipose-derived stem cells via ERK1", 2 MAPK signaling pathway, 2018, pp.51(4), 194~199[DOI]
- Lin LF, "GDNF : a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons", Science, 260, pp.1130~1132 (1993)
- Oppenheim RW, "Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF", Nature, 373, pp.344~346 (1995)
- Chen L-Y, "Targeting the Gdnf gene in peritubular myoid cells disrupts undifferentiated spermatogonial cell development", Proc Natl Acad Sci U S A, 113, pp.1829~1834 (2016)
- Pichel JG, "Defects in enteric innervation and kidney development in mice lacking GDNF", Nature, 382, pp.73~76 (1996)
- Jang HD, "Inactivation of glycogen synthase kinase-3β is required for osteoclast differentiation", J Biol Chem, 286, pp.39043~39050 (2011)
- Zhu H, "A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone", Nat Protoc, 5, pp.550~ (2010)
- Yue PY, "A simplified method for quantifying cell migration", wound healing in 96-well plates, 2010, pp.15, 427~433
- Xiao N, "Glial cell-derived neurotrophic factor promotes dental pulp stem cell migration", J Tissue Eng Regen Med, 12, pp.705~714 (2018)
- 박진희, "RACK1 interaction with c-Src is essential for osteoclast function", Experimental and Molecular Medicine, 51, pp.1~9 (2019), 생화학분자생물학회[DOI]
