# The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

**Authors:** Azadeh Montaseri, Claudia Giampietri, Michela Rossi, Anna Riccioli, Andrea Del Fattore, Antonio Filippini

PMC · DOI: 10.3390/biom10101398 · 2020-09-30

## TL;DR

This review discusses how autophagy, a cellular recycling process, influences osteoclast function and bone health, particularly in conditions like osteoporosis.

## Contribution

The paper consolidates recent findings on autophagy's role in osteoclasts, offering a comprehensive overview of its impact on bone homeostasis.

## Key findings

- Autophagy is essential for osteoclast differentiation and bone resorption.
- Dysregulated autophagy is linked to increased bone loss and osteoporosis.
- Autophagy-related proteins play a key role in maintaining bone homeostasis.

## Abstract

Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue.

## Linked entities

- **Diseases:** osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, Atg7 (autophagy related 7) [NCBI Gene 74244] {aka 1810013K23Rik, Agp7, Apg7l, Atg7l, Gm21553}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, BNIP3 (BCL2 interacting protein 3) [NCBI Gene 664] {aka HABON, NIP3}, Tnfsf11 (tumor necrosis factor (ligand) superfamily, member 11) [NCBI Gene 21943] {aka Ly109l, ODF, OPGL, RANKL, Trance}, OCSTAMP (osteoclast stimulatory transmembrane protein) [NCBI Gene 128506] {aka C20orf123, OC-STAMP, dJ257E24.3}, Map1lc3a (microtubule-associated protein 1 light chain 3 alpha) [NCBI Gene 66734] {aka 1010001H21Rik, 4922501H04Rik, LC3, LC3a}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, ATG5 (autophagy related 5) [NCBI Gene 9474] {aka APG5, APG5-LIKE, APG5L, ASP, SCAR25, hAPG5}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, CYLD (CYLD lysine 63 deubiquitinase) [NCBI Gene 1540] {aka BRSS, CDMT, CYLD1, CYLDI, EAC, FTDALS8}, TRAF3 (TNF receptor associated factor 3) [NCBI Gene 7187] {aka CAP-1, CD40bp, CRAF1, IIAE5, IMD132A, IMD132B}, ATG7 (autophagy related 7) [NCBI Gene 10533] {aka APG7-LIKE, APG7L, GSA7, SCAR31}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, MAP1LC3B (microtubule associated protein 1 light chain 3 beta) [NCBI Gene 81631] {aka ATG8F, LC3B, MAP1A/1BLC3, MAP1LC3B-a}, ATG16L1 (autophagy related 16 like 1) [NCBI Gene 55054] {aka APG16L, ATG16A, ATG16L, IBD10, WDR30}, ZC3H12A (zinc finger CCCH-type containing 12A) [NCBI Gene 80149] {aka MCPIP, MCPIP-1, MCPIP1, Reg1, dJ423B22.1}, DCSTAMP (dendrocyte expressed seven transmembrane protein) [NCBI Gene 81501] {aka FIND, TM7SF4, hDC-STAMP}, ATG12 (autophagy related 12) [NCBI Gene 9140] {aka APG12, APG12L, FBR93, HAPG12}, Trpv4 (transient receptor potential cation channel, subfamily V, member 4) [NCBI Gene 63873] {aka 0610033B08Rik, OTRPC4, Trp12, VR-OAC, VRL-2, VROAC}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, CTSK (cathepsin K) [NCBI Gene 1513] {aka CTS02, CTSO, CTSO1, CTSO2, PKND, PYCD}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, FERMT3 (FERM domain containing kindlin 3) [NCBI Gene 83706] {aka KIND3, MIG-2, MIG2B, UNC112C, URP2, URP2SF}, Trp53 (transformation related protein 53) [NCBI Gene 22059] {aka Tp53, bbl, bfy, bhy, p44, p53}, Becn1 (beclin 1, autophagy related) [NCBI Gene 56208] {aka Atg6}, CSF1R (colony stimulating factor 1 receptor) [NCBI Gene 1436] {aka BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, WDFY3 (WD repeat and FYVE domain containing 3) [NCBI Gene 23001] {aka ALFY, BCHS, MCPH18, ZFYVE25}, Git1 (GIT ArfGAP 1) [NCBI Gene 216963] {aka Cat-1, p95Cat}, Atg5 (autophagy related 5) [NCBI Gene 11793] {aka 2010107M05Rik, 3110067M24Rik, Apg5l, Atg5l, Paddy}, Acp5 (acid phosphatase 5, tartrate resistant) [NCBI Gene 11433] {aka TRACP, TRAP}, RAB7B (RAB7B, member RAS oncogene family) [NCBI Gene 338382] {aka RAB7}, ATG101 (autophagy related 101) [NCBI Gene 60673] {aka C12orf44}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, GABARAPL2 (GABA type A receptor associated protein like 2) [NCBI Gene 11345] {aka ATG8, ATG8C, GATE-16, GATE16, GEF-2, GEF2}, ULK1 (unc-51 like autophagy activating kinase 1) [NCBI Gene 8408] {aka ATG1, ATG1A, UNC51, Unc51.1, hATG1}, Nfatc1 (nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1) [NCBI Gene 18018] {aka 2210017P03Rik, NF-ATc, NFAT2, NFATc, Nfatcb}, TAB2 (TGF-beta activated kinase 1 (MAP3K7) binding protein 2) [NCBI Gene 23118] {aka CHTD2, MAP3K7IP2, TAB-2}, ITGB3 (integrin subunit beta 3) [NCBI Gene 3690] {aka BDPLT16, BDPLT2, BDPLT24, CD61, FMAIT1, GP3A}, ATG14 (autophagy related 14) [NCBI Gene 22863] {aka ATG14L, BARKOR, KIAA0831}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, Cdc42 (cell division cycle 42) [NCBI Gene 12540], CLCN7 (Cl-/H+ antiporter 7) [NCBI Gene 1186] {aka CLC-7, CLC7, HOD, OPTA2, OPTB4, PPP1R63}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, Ctsk (cathepsin K) [NCBI Gene 13038] {aka MMS10-Q, Ms10q, catK}, HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, MAP1LC3A (microtubule associated protein 1 light chain 3 alpha) [NCBI Gene 84557] {aka ATG8E, LC3, LC3A, MAP1ALC3, MAP1BLC3}, Lamp1 (lysosomal-associated membrane protein 1) [NCBI Gene 16783] {aka CD107a, LGP-120, LGP-A, Lamp-1, P2B, Perk}, MIR20A (microRNA 20a) [NCBI Gene 406982] {aka C13orf25, MIR20, MIRH1, MIRHG1, MIRN20, MIRN20A}
- **Diseases:** hypoxic (MESH:D002534), osteoporotic (MESH:D058866), bone erosion (MESH:D014077), Renal transplanted (MESH:D007674), heart disease (MESH:D006331), vascular calcification (MESH:D061205), rheumatoid arthritis (MESH:D001172), anxiety (MESH:D001007), osteopenia (MESH:D001851), cancer (MESH:D009369), bone (MESH:D001847), hypoxia (MESH:D000860), tooth eruption (MESH:D014079), impairment of bone mineralization (MESH:D012080), infection (MESH:D007239), skeletal diseases (MESH:D004194), neurodegenerative diseases (MESH:D019636), bone fracture (MESH:D050723), Osteoporosis (MESH:D010024), Paget's disease of bone (MESH:D010001), bone resorption (MESH:D001862), estrogen deficiency (MESH:D056828), calcification (MESH:D002114), Paget's disease (MESH:C537701), fragility fracture (MESH:D005600), inflamm-aging (MESH:D007249)
- **Chemicals:** cyclic GMP-AMP (MESH:C584311), oxygen (MESH:D010100), phosphatidylinositol 3-phosphate (MESH:C055525), nucleotides (MESH:D009711), 1a,25-(OH)2 Vitamin D3 (-), steroid (MESH:D013256), sphingosine-1-phosphate (MESH:C060506), Cl- (MESH:D002713), amino acids (MESH:D000596), lipopolysaccharide (MESH:D008070), hydroxyapatite (MESH:D017886), calcium (MESH:D002118), phosphatidylethanolamine (MESH:C483858), 3-methyladenine (MESH:C025946), rapamycin (MESH:D020123), phosphate (MESH:D010710), lipid (MESH:D008055), chloroquine (MESH:D002738)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** A1, S1P, R714C

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7601508/full.md

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Source: https://tomesphere.com/paper/PMC7601508