Break and then stand: novel insight into osteoclast functions in the skeletal system
- Journal of Army Medical University Vol. 44, Issue 1, Pages: 79-88(2022)
- 作者机构：
400038 重庆，陆军军医大学（第三军医大学）生物医学工程与影像医学系生物医学材料学教研室，组织工程国家/地方联合工程实验室
- 作者简介：
- 基金信息：the Key Program of National Natural Science Foundation of China(81930067);the General Program of National Natural Science Foundation of China(31870962);the Medical Science and Technology Youth Cultivation Project of PLA(20QNPY022)
DOI：10.16016/j.1000-5404.202112049
CLC： R336Received：01 December 2021，
Revised：2021-12-14，
Published：15 January 2022
- 稿件说明：
移动端阅览
Shiwu DONG, Wenhui HU. Break and then stand: novel insight into osteoclast functions in the skeletal system[J]. Journal of Army Medical University, 2022, 44(1): 79-88.
Shiwu DONG, Wenhui HU. Break and then stand: novel insight into osteoclast functions in the skeletal system[J]. Journal of Army Medical University, 2022, 44(1): 79-88. DOI： 10.16016/j.1000-5404.202112049.
摘要
骨骼系统为支撑身体、协调躯体运动、控制矿物质稳态和造血提供了重要的基础。破骨细胞是由单核/巨噬细胞造血谱系前体细胞融合而成的特化细胞，在骨稳态和健康维持中至关重要。已有大量实验证实其细胞形成和功能失调与骨质疏松症、骨折愈合、骨关节炎和原发性/转移性骨肿瘤等密切相关。一直以来，破骨细胞作为“噬骨者（bone eaters）”被聚焦于探讨其在骨稳态和疾病中的角色。近年来，随着单细胞标记和检测技术的快速发展并在骨领域中的广泛应用，新的“破骨细胞亚型”概念及其功能不断得到解析和完善。骨微环境稳态是破骨细胞及其主导的细胞网络共同活动的结果；从细胞网络出发，系统阐释破骨细胞与骨/关节疾病的内在关系，才能更好地理解疾病的本质。“破而后立”——是本课题组所提出通过调控破骨细胞来重建骨微环境稳态、以延缓骨/关节疾病进程的新理念。同时，将“破骨细胞”概念引入传统组织工程骨与软骨构筑技术，有望实现骨/软骨疾病干预和再生修复的综合应用。
Abstract
The skeleton provides the scaffold to support body weight
enable body movement
control mineral homeostasis
and provide the location for hematopoiesis. Osteoclasts are specialized cells formed by the fusion of committed monocyte/macrophage hematopoietic lineage precursor cells. The importance of osteoclasts in bone homeostasis and health is evidenced by the diseases in which osteoclast formation and function are dysregulated
such as osteoporosis
fracture healing
osteoarthritis
and primary/metastatic bone cancer. All the time
osteoclasts
as "bone eaters"
are focused on exploring their role in bone homeostasis and diseases. With the development of single cell labeling and detection technologies and their wide application in the field of bone
the novel concept of osteoclast subtypes and their emerging functions have been continuously uncovered and improved. Cell-cell communication network coordinated by osteoclasts balances bone microenvironment
therefore
from the perspective of network
interpreting the relationship between osteoclasts and bone/joint diseases will help to understand the nature of the diseases better. Finally
we propose osteoclasts controlling-based strategies for rebuilding microenvironmental homeostasis
aiming to bone/cartilage disease intervention and regenerative repair.
关键词
Keywords
references
KIM J M, LIN C J, STAVRE Z, et al . Osteoblast-osteoclast communication and bone homeostasis[J ] . Cell, 2020, 9(9): E2073. DOI: 10.3390/cells9092073.
TATEIWA D, YOSHIKAWA H, KAITO T. Cartilage and bone destruction in arthritis: pathogenesis and treatment strategy: a literature review[J]. Cell, 2019, 8(8): E818. DOI: 10.3390/cells8080818.
OKAMOTO K, NAKASHIMA T, SHINOHARA M, et al . Osteoimmunology: the conceptual framework unifying the immune and skeletal systems[J ] . Physiol Rev, 2017, 97(4): 1295-1349. DOI: 10.1152/physrev.00036.2016.
BOYLE W J, SIMONET W S, LACEY D L. Osteoclast differentiation and activation[J]. Nature, 2003, 423(6937): 337-342. DOI: 10.1038/nature01658.
YAGI M, MIYAMOTO T, TOYAMA Y, et al . Role of DCSTAMP in cellular fusion of osteoclasts and macrophage giant cells[J ] . J Bone Miner Metab, 2006, 24(5): 355-358. DOI: 10.1007/s0077400606979.
BROUNAIS B, RUIZ C, ROUSSEAU J, et al . Novel anticancer strategy in bone tumors by targeting molecular and cellular modulators of bone resorption[J ] . Recent Pat Anticancer Drug Discov, 2008, 3(3): 178-186. DOI: 10.2174/157489208786242269.
CHARLES J F, ALIPRANTIS A O. Osteoclasts: more than 'bone eaters'[J]. Trends Mol Med, 2014, 20(8): 449-459. DOI: 10.1016/j.molmed.2014.06.001.
WANG T, LIU Q, TJHIOE W, et al . Therapeutic potential and outlook of alternative medicine for osteoporosis[J ] . Curr Drug Targets, 2017, 18(9): 1051-1068. DOI: 10.2174/1389450118666170321105425.
KARSDAL M A, BAYJENSEN A C, LORIES R J, et al . The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?[J ] . Ann Rheum Dis, 2014, 73(2): 336-348. DOI: 10.1136/annrheumdis2013204111.
UDAGAWA N, KOIDE M, NAKAMURA M, et al . Osteoclast differentiation by RANKL and OPG signaling pathways[J ] . J Bone Miner Metab, 2021, 39(1): 19-26. DOI: 10.1007/s00774020011626.
TAKAYANAGI H. RANKL as the master regulator of osteoclast differentiation[J]. J Bone Miner Metab, 2021, 39(1): 13-18. DOI: 10.1007/s00774020011911.
BOYCE B F. Advances in the regulation of osteoclasts and osteoclast functions[J]. J Dent Res, 2013, 92(10): 860-867. DOI: 10.1177/0022034513500306.
WADA T, NAKASHIMA T, HIROSHI N, et al . RANKLRANK signaling in osteoclastogenesis and bone disease[J ] . Trends Mol Med, 2006, 12(1): 17-25. DOI: 10.1016/j.molmed.2005.11.007.
BATTAGLINO R, KIM D, FU J, et al . Cmyc is required for osteoclast differentiation[J ] . J Bone Miner Res, 2002, 17(5): 763-773. DOI: 10.1359/jbmr.2002.17.5.763.
MIYAMOTO T. Regulators of osteoclast differentiation and cellcell fusion[J]. Keio J Med, 2011, 60(4): 101-105. DOI: 10.2302/kjm.60.101.
VIGNERY A. Osteoclasts and giant cells: macrophage-macrophage fusion mechanism[J]. Int J Exp Pathol, 2000, 81(5): 291-304. DOI: 10.1111/j.13652613.2000.00164.x.
LEE J H, HSIEH C F, LIU H W, et al . Lipid raftassociated stomatin enhances cell fusion[J ] . FASEB J, 2017, 31(1): 47-59. DOI: 10.1096/fj.201600643r.
DOU C, ZHANG C C, KANG F, et al . MiR7b directly targets DCSTAMP causing suppression of NFATc 1 and cFos signaling during osteoclast fusion and differentiation[J ] . Biochim Biophys Acta Gene Regul Mech, 2014, 1839(11): 1084-1096. DOI: 10.1016/j.bbagrm.2014.08.002..
ELONHEIMO H, LANGE R, TOLONEN H, et al . Environmental substances associated with osteoporosis—A scoping review[J ] . Int J Environ Res Public Heal, 2021, 18(2): 738. DOI: 10.3390/ijerph18020738.
BLANGY A, BOMPARD G, GUERIT D, et al . The osteoclast cytoskeletoncurrent understanding and therapeutic perspectives for osteoporosis[J ] . J Cell Sci, 2020, 133(13): jcs244798. DOI: 10.1242/jcs.244798.
TAKEYAMA K , CHATANI M, TAKANO Y, et al . In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts[J ] . Dev Biol, 2014, 394(2): 292-304. DOI: 10.1016/j.ydbio.2014.08.007..
HE L H, LIU M, HE Y, et al . TRPV 1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation[J ] . Sci Rep, 2017, 7: 42385. DOI: 10.1038/srep42385..
HUNTER D J, BIERMAZEINSTRA S. Osteoarthritis[J]. Lancet, 2019, 393(10182): 1745-1759. DOI: 10.1016/s01406736(19)304179.
FANG C, GUO J W, WANG Y J, et al . Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK/cfos/NFATc 1 pathway, and subsequently inhibiting subchondral osteoclast fusion[J ] . Acta Pharmacol Sin, 2021: 1-12. DOI: 10.1038/s41401021007479..
YILDIRIM M, BAYKARA M. Differentiation of multiple myeloma and lytic bone metastases: histogram analysis[J]. J Comput Assist Tomogr, 2020, 44(6): 953-955. DOI: 10.1097/rct.0000000000001086.
MAURIZI A, RUCCI N. The osteoclast in bone metastasis: player and target[J]. Cancers (Basel), 2018, 10(7): 218. DOI: 10.3390/cancers10070218.
XIE H, CUI Z, WANG L, et al . PDGFBB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis[J ] . Nat Med, 2014, 20(11): 1270-1278. DOI: 10.1038/nm.3668.
GAO B, DENG R, CHAI Y, et al . Macrophagelineage TRAP+ cells recruit periosteumderived cells for periosteal osteogenesis and regeneration[J ] . J Clin Invest, 2019, 129(6): 2578-2594. DOI: 10.1172/jci98857.
BAI Y, YU T, DENG J Z, et al . Connective tissue growth factor from periosteal tartrate acid phosphatasepositive monocytes direct skeletal stem cell renewal and fate during bone healing[J ] . Front Cell Dev Biol, 2021, 9: 730095. DOI: 10.3389/fcell.2021.730095.
ROMEO S G, ALAWI K M, RODRIGUES J, et al . Endothelial proteolytic activity and interaction with nonresorbing osteoclasts mediate bone elongation[J ] . Nat Cell Biol, 2019, 21(4): 430-441. DOI: 10.1038/s4155601903047.
FERGUSON C, ALPERN E, MICLAU T, et al . Does adult fracture repair recapitulate embryonic ske letal formation?[J ] .Mech Dev, 1999, 87(1/2): 57-66. DOI: 10.1016/s09254773(99)001422.
GOLDRING S R. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis[J]. Rheumatology (Oxford), 2003, 42(Suppl 2): ii11-ii16. DOI: 10.1093/rheumatology/keg327.
YUAN F L, WU Q Y, MIAO Z N, et al . Osteoclast-derived extracellular vesicles: novel regulators of osteoclast-ogenesis and osteoclast-osteoblasts communication in bone remodeling[J ] . Front Physiol, 2018, 9: 628. DOI: 10.3389/fphys.2018.00628.
MA Q Y, LIANG M M, LIMJUNYAWONG N, et al . Osteoclastderived apoptotic bodies show extended biological effects of parental cell in promoting bone defect healing[J ] . Theranostics, 2020, 10(15): 6825-6838. DOI: 10.7150/thno.45170.
MA Q Y, LIANG M M, WU Y T, et al . Osteoclastderived apoptotic bodies couple bone resorption and formation in bone remodeling[J ] . Bone Res, 2021, 9(1): 5. DOI: 10.1038/s41413020001211.
TSOURDI E, LANGDAHL B, COHENSOLAL M, et al . Discontinuation of Denosumab therapy for osteoporosis: a systematic review and position statement by ECT S[J ] . Bone, 2017, 105: 11-17. DOI: 10.1016/j.bone.2017.08.003.
MCDONALD M M, KHOO W H, NG P Y, et al . Osteoclasts recycle via osteomorphs during RANKLstimulated bone resorption[J ] . Cell, 2021, 184(7): 1940. DOI: 10.1016/j.cell.2021.03.010..
OKAMOTO K, TAKAYANAGI H. Osteoimmunology[J]. Cold Spring Harb Perspect Med, 2019, 9(1): a031245. DOI: 10.1101/cshperspect.a031245.
TSUKASAKI M, TAKAYANAGI H. Osteoimmunology: evolving concepts in boneimmune interactions in health and disease[J]. Nat Rev Immunol, 2019, 19(10): 626-642. DOI: 10.1038/s4157701901788.
NARISAWA M, KUBO S, OKADA Y, et al . Human dendritic cellderived osteoclasts with high bone resorption capacity and T cell stimulation ability[J ] . Bone, 2021, 142: 115616. DOI: 10.1016/j.bone.2020.115616.
LAPÉRINE O, BLINWAKKACH C, GUICHEUX J, et al . Dendritic-cell-derived osteoclasts: a new game changer in bone-resorption-associated diseases[J ] . Drug Discov Today, 2016, 21(9): 1345-1354. DOI: 10.1016/j.drudis.2016.04.022.
LI H Y, HONG S, QIAN J F, et al . Cross talk between the bone and immune systems: osteoclasts function as antigenpresenting cells and activate CD4 + and CD8 + T cells[J ] . Blood, 2010, 116(2): 210-217. DOI: 10.1182/blood200911255026..
PENG Y, WU S, LI Y S, et al . Type H blood vessels in bone modeling and remodeling[J ] . Theranostics, 2020, 10(1): 426-436. DOI: 10.7150/thno.34126.
YU W, ZHONG L L, YAO L T, et al . Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss[J ] . J Clin Invest, 2021, 131(2): 140214. DOI: 10.1172/JCI140214.
ZHONG L,YAO L,TOWER R J, et al .Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment[J ] . Elife,2020,9. DOI: 10.7554/elife.54695.DOI:10.7554/elife.54695.
BYRNE N M, SUMMERS M A, MCDONALD M M. Tumor cell dormancy and reactivation in bone: skeletal biology and therapeutic opportunities[J]. JBMR Plus, 2019, 3(3): e10125. DOI: 10.1002/jbm4.10125.
HIGGINBOTHAM J N, DEMORY BECKLER M, GEPHART J D, et al . Amphiregulin exosomes increase cancercell invasion[J ] . Curr Biol, 2011, 21(9): 779-786. DOI: 10.1016/j.cub.2011.03.043.
TIEDEMANN K, SADVAKASSOVA G, MIKOLAJEWICZ N, et al . Exosomal release of Lplastin by breast cancer cells facilitates metastatic bone osteolysis[J ] . Transl Oncol, 2019, 12(3): 462-474. DOI: 10.1016/j.tranon.2018.11.014.
YANG Z F, YUE Z Y, MA X R, et al . Calcium homeostasis: a potential vicious cycle of bone metastasis in breast cancers[J ] . Front Oncol, 2020, 10: 293. DOI: 10.3389/fonc.2020.00293.
TAI Y T, CHO S F, ANDERSON K C. Osteoclast immunosuppressive effects in multiple myeloma: role of programmed cell death ligand 1[J]. Front Immunol, 2018, 9: 1822. DOI: 10.3389/fimmu.2018.01822.
WANG K Y, GU Y, LIAO Y H, et al . PD1 blockade inhibits osteoclast formation and murine bone cancer pain[J ] . J Clin Invest, 2020, 130(7): 3603-3620. DOI: 10.1172/JCI133334.
AN G, ACHARYA C, FENG X Y, et al . Osteoclasts promot e immune suppressive microenvironment in multiple myeloma: therapeutic implication[J ] . Blood, 2016, 128(12): 1590-1603. DOI: 10.1182/blood201603707547.
DAI J J, DONG R, HAN X Y, et al . Osteoclastderived exosomal let7a5p targets Smad2 to promote the hypertrophic differentiation of chondrocytes[J ] . Am J Physiol Cell Physiol, 2020, 10.1152/ajpcell. 00039.2020. DOI: 10.1152/ajpcell.00039.2020.
LU J S, ZHANG H Y, CAI D Z, et al . Positivefeedback regulation of subchondral Htype vessel formation by chondrocyte promotes osteoarthritis development in mice[J ] . J Bone Miner Res, 2018, 33(5): 909-920. DOI: 10.1002/jbmr.3388.
HU W H, CHEN Y Q, DOU C, et al . Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis[J ] . Ann Rheum Dis, 2020, 80(4): 413-422. DOI: 10.1136/annrheumdis2020218089.
LIU J, WU X H, LU J, et al . Exosomal transfer of osteoclastderived miRNAs to chondrocytes contributes to 〖JP2〗osteoarthritis progression[J ] . Nat Aging, 2021, 1(4): 368-384. DOI: 10.1038/s43587021000506.
ZHEN G H, DAN Y, WANG R M, et al . An antibody against Siglec15 promotes bone formation and fracture healing by increasing TRAP + mononuclear cells and PDGFBB secretion[J ] . Bone Res, 2021, 9(1): 47. DOI: 10.1038/s41413021001611..
DOU C, LI J M, HE J, et al . Bonetargeted pHresponsive cerium nanoparticles for anabolic therapy in osteoporosis[J ] . Bioact Mater, 2021, 6(12): 4697-4706. DOI: 10.1016/j.bioactmat.2021.04.038.
DONG R, BAI Y, DAI J J, et al . Engineered scaffolds based on mesenchymal stem cells/preosteoclasts extracellular matrix promote bone regeneration[J ] . J Tissue Eng, 2020, 11: 2041731420926918. DOI: 10.1177/2041731420926918.
DENG C, ZHU H, LI J, et al . Bioactive scaffolds for regeneration of cartilage and subchondral bone interface[J ] . Theranostics, 2018, 8(7): 1940-1955. DOI:10.7150/thno.23674.
0
Views
0
下载量
0
CSCD
- L-PDFDownload
- Meta-XMLDownload
- BibTeXDownload
- EndnoteDownload
- RefMan Download
- NoteExpressDownload
- NoteFirstDownload
Publicity Resources
Related Articles
Related Author
Related Institution
- Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19
京公网安备11010802024621 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.
