PMID- 38463697
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240312
IS  - 2573-9832 (Electronic)
IS  - 2573-9832 (Linking)
VI  - 6
IP  - 3
DP  - 2024 Mar
TI  - Loss of chaperone-mediated autophagy does not alter age-related bone loss in male 
      mice.
PG  - 73-84
LID - 10.1096/fba.2023-00133 [doi]
AB  - Chaperone-mediated autophagy (CMA) is a lysosome-dependent degradation pathway 
      that eliminates proteins that are damaged, partially unfolded, or targeted for 
      selective proteome remodeling. CMA contributes to several cellular processes, 
      including stress response and proteostasis. Age-associated increase in cellular 
      stressors and decrease in CMA contribute to pathologies associated with aging in 
      various tissues. CMA contributes to bone homeostasis in young mice. An 
      age-associated reduction in CMA was reported in osteoblast lineage cells; 
      however, whether declining CMA contributes to skeletal aging is unknown. Herein 
      we show that cellular stressors stimulate CMA in UAMS-32 osteoblastic cells. 
      Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, 
      sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and 
      oxidative stress. As elevations in these stressors are thought to contribute to 
      age-related bone loss, we hypothesized that declining CMA contributes to the 
      age-associated decline in bone formation by sensitizing osteoblast lineage cells 
      to elevated stressors. To test this, we aged male CMA-deficient mice and controls 
      up to 24 months of age and examined age-associated changes in bone mass and 
      architecture. We showed that lack of CMA did not alter age-associated decline in 
      bone mineral density as measured by dual x-ray absorptiometry (DXA). Moreover, 
      microCT analysis performed at 24 months of age showed that vertebral cancellous 
      bone volume, cortical thickness, and porosity of CMA-deficient and control mice 
      were similar. Taken together, these results suggest that reduction of CMA does 
      not contribute to age-related bone loss.
CI  - (c)2024 The Authors FASEB BioAdvances published by The Federation of American 
      Societies for Experimental Biology.
FAU - Hendrixson, James A
AU  - Hendrixson JA
AUID- ORCID: 0009-0004-5175-2357
AD  - Department of Physiology and Cell Biology University of Arkansas for Medical 
      Sciences Little Rock Arkansas USA.
FAU - James, Alicen
AU  - James A
AUID- ORCID: 0009-0006-4750-4419
AD  - Department of Physiology and Cell Biology University of Arkansas for Medical 
      Sciences Little Rock Arkansas USA.
FAU - Akel, Nisreen S
AU  - Akel NS
AUID- ORCID: 0009-0007-7326-7020
AD  - Department of Physiology and Cell Biology University of Arkansas for Medical 
      Sciences Little Rock Arkansas USA.
FAU - Laster, Dominique J
AU  - Laster DJ
AUID- ORCID: 0009-0008-1285-2020
AD  - Department of Physiology and Cell Biology University of Arkansas for Medical 
      Sciences Little Rock Arkansas USA.
FAU - Crawford, Julie A
AU  - Crawford JA
AUID- ORCID: 0000-0002-8167-8627
AD  - Center for Musculoskeletal Disease Research (CMDR) University of Arkansas for 
      Medical Sciences Little Rock Arkansas USA.
AD  - Division of Endocrinology University of Arkansas for Medical Sciences Little Rock 
      Arkansas USA.
FAU - Berryhill, Stuart B
AU  - Berryhill SB
AUID- ORCID: 0009-0003-5119-1062
AD  - Center for Musculoskeletal Disease Research (CMDR) University of Arkansas for 
      Medical Sciences Little Rock Arkansas USA.
AD  - Division of Endocrinology University of Arkansas for Medical Sciences Little Rock 
      Arkansas USA.
FAU - Onal, Melda
AU  - Onal M
AUID- ORCID: 0000-0002-5804-495X
AD  - Department of Physiology and Cell Biology University of Arkansas for Medical 
      Sciences Little Rock Arkansas USA.
LA  - eng
PT  - Journal Article
DEP - 20240220
PL  - United States
TA  - FASEB Bioadv
JT  - FASEB bioAdvances
JID - 101733210
PMC - PMC10918985
OTO - NOTNLM
OT  - CMA
OT  - age-related bone loss
OT  - aging
OT  - cellular stress
OT  - chaperone-mediated autophagy
OT  - skeletal aging
EDAT- 2024/03/11 06:43
MHDA- 2024/03/11 06:44
PMCR- 2024/02/20
CRDT- 2024/03/11 04:26
PHST- 2023/11/10 00:00 [received]
PHST- 2024/01/18 00:00 [revised]
PHST- 2024/02/06 00:00 [accepted]
PHST- 2024/03/11 06:44 [medline]
PHST- 2024/03/11 06:43 [pubmed]
PHST- 2024/03/11 04:26 [entrez]
PHST- 2024/02/20 00:00 [pmc-release]
AID - FBA21426 [pii]
AID - 10.1096/fba.2023-00133 [doi]
PST - epublish
SO  - FASEB Bioadv. 2024 Feb 20;6(3):73-84. doi: 10.1096/fba.2023-00133. eCollection 
      2024 Mar.