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Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA
Open accessAbstract
Osteoarthritis (OA) is the most prevalent joint disease, but neither preventive measures nor disease-modifying drugs are available and a continuing need exists for safe and effective symptom-modifying therapies. Clinical trials of candidate disease-modifying OA drugs in patients with established or advanced disease have not demonstrated their efficacy, but these failed trials have motivated investigation into the mechanisms that maintain joint health. The enhancement of such mechanisms could be a novel approach to reducing the risk of OA. Aging is one of the most important risk factors for OA; however, aging of joint cartilage is a process that is distinct from the subsequent cartilage changes that develop following the onset of OA. This Review focuses on the mechanisms that maintain cell and tissue homeostasis, and how these mechanisms fail during the aging process. Autophagy is a cellular homeostasis mechanism for the removal of dysfunctional organelles and macromolecules. Defective autophagy is involved in the pathogenesis of aging-related diseases and recent observations indicate that this process is compromised in aging cartilage. Augmentation of homeostasis mechanisms is discussed as a novel avenue to delay joint aging and reduce OA risk.
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Zhang, F., Wang, J., Chu, J., Yang, C., Xiao, H., Zhao, C., Sun, Z., Gao, X., Chen, G., Han, Z., et al. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000438513 · Cited by 68
Zhang, H., Zheng, W., Du, L., & Zheng, J. (2021) · Cartilage · doi:10.1177/19476035211023550 · Cited by 70
Ansari, M. Y., Ahmad, N., & Haqqi, T. M. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000493225 · Cited by 62
Khan, N. M., Ansari, M. Y., & Haqqi, T. M. (2016) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25750 · Cited by 62
“Earlier studies suggested that activation of autophagy appears to be beneficial in joint disease and protect against the development of OA [Lotz and Carames, 2011].”
BackgroundÁlvarez-García, Ó., Olmer, M., Akagi, R., Akasaki, Y., Fisch, K. M., Shen, T., Su, A. I., & Lotz, M. (2016) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2016.04.015 · Cited by 60
“Recent evidence supports a central role of autophagy in cartilage homeostasis and OA development 36 .”
BackgroundBNIP3-Dependent Mitophagy via PGC1α Promotes Cartilage Degradation
Kim, D., Song, J., & Jin, E. (2021) · Cells · doi:10.3390/cells10071839 · Cited by 56
“Autophagy may play a crucial role in maintaining cartilage homeostasis and the deregulation of autophagy could contribute to cartilage degradation, a hallmark of OA pathogenesis [20].”
BackgroundLiu, Y., Zhu, H., Yan, X., Gu, H.-Y., Gu, Z., & Liu, F. (2017) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2017.07.094 · Cited by 52
Wei, Y., Wang, Y., Wang, Y., & Bai, L. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477387 · Cited by 55
ZHANG, Z. M., Shen, C., Li, H., FAN, Q., Ding, J., JIN, F. C., & Sha, L. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4970 · Cited by 54
Chen, C., Kuo, S. M., Tien, Y.-C., Shen, P., Kuo, Y.-W., & Huang, H. H. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s252223 · Cited by 54
Dhanabalan, K. M., Dravid, A. A., Agarwal, S., Sharath, R. K., Padmanabhan, A. K., & Agarwal, R. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10298 · Cited by 53
“Autophagy is a stress survival mechanism that gets activated as an adaptive process to different forms of metabolic stress, and the role of autophagy in OA is widely studied.(8,12,15) Cellular senescence is another growing field and is an important target for many diseases, including OA.”
BackgroundLiao, S., Zheng, Q., Shen, H., Yang, G., Xu, Y., Zhang, X., Ouyang, H., & Pan, Z. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42369 · Cited by 53
Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities
Ramasamy, T. S., Yee, Y. M., & Khan, I. M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.625497 · Cited by 52
Shen, T., Álvarez-García, Ó., Li, Y.-K., Olmer, M., & Lotz, M. K. (2016) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2016.09.017 · Cited by 52
Jayaram, P., Yeh, P. C., Patel, S., Cela, R., Shybut, T. B., Grol, M. W., & Lee, B. (2019) · The American Journal of Sports Medicine · doi:10.1177/0363546519827294 · Cited by 52
“Importantly, although analysis of frozen aliquots of PRP was previously reported in the literature, this is more representative of platelet lysate.(1,2,4,9,10,18,19) While the literature cites meaningful information with the use of platelet lysates, it is not typically used in peripheral joint applications.”
BackgroundResultInfluentialNutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role
D’Adamo, S., Cetrullo, S., Panichi, V., Mariani, E., Flamigni, F., & Borzı̀, R. M. (2020) · Cells · doi:10.3390/cells9051232 · Cited by 52
“An additional pathway to counteract cartilage derangement is via the promotion of autophagy [39], i.”
BackgroundLee, D.-Y., Park, Y., Song, M.-G., Kim, D. R., Zada, S., & Kim, D. (2020) · Antioxidants · doi:10.3390/antiox9010083 · Cited by 53
FGF2: A Key Regulator Augmenting Tendon-to-Bone Healing and Cartilage Repair
Zhang, J., Liu, Z., Li, Y., You, Q., Yang, J., Jin, Y. H., Zou, G., Tang, J., Ge, Z., & Liu, Y. (2020) · Regenerative Medicine · doi:10.2217/rme-2019-0080 · Cited by 49
Integrin signalling in joint development, homeostasis and osteoarthritis
Miao, M. Z., Lee, J. S., Yamada, K. M., & Loeser, R. F. (2024) · Nature Reviews Rheumatology · doi:10.1038/s41584-024-01130-8 · Cited by 56
Zhao, X., Li, H., & Wang, L. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.03.005 · Cited by 48
RetractedDefective autophagy in chondrocytes with Kashin-Beck disease but higher than osteoarthritis
Wu, C., Zheng, J., Yao, X., Shan, H., Li, Y., Xu, P., & Guo, X. (2014) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2014.08.010 · Cited by 47
Jiang, L., Lee, S., Wang, Y., Xu, Q., Meng, D., & Zhang, J. (2016) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.12.021 · Cited by 46
Dhanabalan, K. M., Gupta, V. K., & Agarwal, R. (2020) · Biomaterials Science · doi:10.1039/d0bm00596g · Cited by 46
D’Adamo, S., Cetrullo, S., Minguzzi, M., Silvestri, Y., Borzı̀, R. M., & Flamigni, F. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/3720128 · Cited by 45
“Autophagy failure contributes to OA pathogenesis and is responsible for the accumulation of cellular defects in chondrocytes [11, 12].”
BackgroundRole of TLR2 and TLR4 in regulation of articular chondrocyte homeostasis
Wang, Y., Zhao, X., & Liu‐Bryan, R. (2020) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2020.01.011 · Cited by 44
“autophagy have been shown to involve in regulation of chondrocyte homeostasis, and their dysfunction is associated with OA (9,10), we studied the cellular stress responses in chondrocytes deficient in TLR2 and TLR4 in vitro.”
BackgroundCai, H., Wang, P., Yang, X., Yao, Y. D., Liu, J., Li, T., Sun, Y., Liang, J., Fan, Y., & Zhang, X. (2019) · Regenerative Biomaterials · doi:10.1093/rb/rbz028 · Cited by 44
“PCs would endow the cartilage with a certain capacity for self-renewal under mechanical abrasion [6, 7].”
BackgroundInfluentialBhattacharjee, M., Ivirico, J. L. E., Kan, H.-M., Bordett, R., Pandey, R., Otsuka, T., Nair, L. S., & Laurencin, C. T. (2020) · Scientific Reports · doi:10.1038/s41598-020-75921-w · Cited by 44
Metadata
- Authors
- Lotz, M. K., & Caramés, B.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Lotz, Martin K.
- Venue
- Nature Reviews Rheumatology
- Published
- 2011-08-02
- Volume
- 7
- Issue
- 10
- Pages
- 579-587
- ISSN
- 1759-4790 (ISSN-L)
- 1759-4804
- PMC
- PMC3192496
- OpenAlex
- W1985004392
- Cited by
- 314
- References
- 99
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 32 · 2023: 27 · 2022: 27 · 2021: 27 · 2020: 29 · 2019: 23 · 2018: 14 · 2017: 13 · 2016: 20 · 2015: 19 · 2014: 16 · 2013: 20 · 2012: 11
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01AG007996, AG-007996)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR056026, R01AR056026)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Surgery › Hip disorders and treatments
- Keywords
- autophagy, cartilage homeostasis, osteoarthritis, joint aging, cartilage aging, disease-modifying osteoarthritis drugs, joint health, age-related diseases
- MeSH terms
- Aging, Animals, Autophagy, Cartilage, Articular, Homeostasis, Humans, Osteoarthritis
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