Cited by 314Osteoarthritis Treatment and MechanismsAutophagy in Disease and TherapyHip disorders and treatments

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Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA

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Lotz, Martin K., Caramés, Beatriz·2011·Nature Reviews Rheumatology

DOI 10.1038/nrrheum.2011.109PMC PMC3192496

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Abstract

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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Background
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Background
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Hasegawa, A., Yonezawa, T., Taniguchi, N., Otabe, K., Akasaki, Y., Matsukawa, T., Saito, M., Neo, M., Marmorstein, L. Y., & Lotz, M. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39963 · Cited by 39
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Background
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Background
Double-stranded RNA released from damaged articular chondrocytes promotes cartilage degeneration via Toll-like receptor 3-interleukin-33 pathway
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Background
The impact of ageing mechanisms on musculoskeletal system diseases in the elderly
Cai, Y., Han, Z., Cheng, H., Li, H., Wang, K., Chen, J., Liu, Z., Xie, Y., Lin, Y., Zhou, S., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1405621 · Cited by 51
“…of FOXO activity induces musculoskeletal-related diseases, and autophagic gene expression is signi ﬁ cantly lower in the cartilage of elderly osteoarthritis patients, demonstrating that reduced autophagic activity in cartilage tissue leads to the development of cartilage degeneration (63, 64).”
Background
Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis
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“Autophagy is an important survival mechanism in normal chondrocytes and in response to stress (Lotz and Carames 2011).”
Background
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Background
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Loss of Vhl in cartilage accelerated the progression of age-associated and surgically induced murine osteoarthritis
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“Autophagy is an important mechanism for the removal of dysfunctional organelles and macromolecules and maintaining cartilage homeostasis, and this function is compromised in aging cartilage [25].”
Background
CircSLC7A2 protects against osteoarthritis through inhibition of the miR‐4498/TIMP3 axis
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Background
Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment
Sun, H., Wu, Y. R., Pan, Z., Yu, D., Chen, P., Zhang, X., Wu, H., Zhang, X., An, C., Chen, Y., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.06.002 · Cited by 34
“While autophagy was previously demonstrated to be essential in cartilage homeostasis maintenance, [38] OA progression, [28, 39, 40] and several reports illustrated that inhibition of EGFR up-regulated autophagy in tumor cells, [41, 42] our results, together with previous research findings, connected the missing linkag…”
Result
Compromised autophagy precedes meniscus degeneration and cartilage damage in mice
Meckes, J. K., Caramés, B., Olmer, M., Kiosses, W. B., Grogan, S. P., Lotz, M. K., & DʼLima, D. D. (2017) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2017.07.023 · Cited by 33
P62: An emerging oncotarget for osteolytic metastasis
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Background
Achyranthes bidentata polysaccharides induce chondrocyte proliferation via the promotion of the G1/S cell cycle transition
YU, F., Li, X., CAI, L., Li, H., Chen, J., WONG, X., Xu, H., Zheng, C., Liu, X., & Ye, H. (2013) · Molecular Medicine Reports · doi:10.3892/mmr.2013.1286 · Cited by 32
Saturated fatty acids promote chondrocyte matrix remodeling through reprogramming of autophagy pathways
Sekar, S., Wu, X., Friis, T., Crawford, R., Prasadam, I., & Xiao, Y. (2018) · Nutrition · doi:10.1016/j.nut.2018.02.018 · Cited by 32
“In order to survive, cells in such tissues depend on a 73 mechanism called autophagy to remove the damaged organelles and macromolecules (8).”
Background
20-Deoxyingenol alleviates osteoarthritis by activating TFEB in chondrocytes
Gu, M., Jin, J., Ren, C., Chen, X., Pan, Z., Wu, Y., Tian, N., Sun, L., Wu, A., Gao, W., et al. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2020.105361 · Cited by 33
Transcriptomic analyses of joint tissues during osteoarthritis development in a rat model reveal dysregulated mechanotransduction and extracellular matrix pathways
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“…leading to posttraumatic OA (PTOA) 1 or by a series of risk factors, including excessive mechanical load 2,3 , which during aging manifest their effects through decompensation of cellular homeostasis mechanisms 4 and subsequent joint in ﬂ ammation, pain and structural damage to the joint tissues.”
Background
Cyst formation in the subchondral bone following cartilage repair
Gao, L., Cucchiarini, M., & Madry, H. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.248 · Cited by 33
Mechanisms and models of endoplasmic reticulum stress in chondrodysplasia
Patterson, S. E., & Dealy, C. N. (2014) · Developmental Dynamics · doi:10.1002/dvdy.24131 · Cited by 30
“…pathways such as autophagy have been suggested to be required for appropriate homeostatic maintenance of the articular cartilage of the joints (Lotz and Carames, 2011; Chang et al., 2013), excessive activation of ER stress and UPR responses in articular cartilage have been correlated with…”
Background
Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines
Lo, W., Chen, W.-H., Lin, T., Hwang, S., Zeng, R., Hsu, W.-C., Chiang, Y.-M., Liu, M.-C., Williams, D. F., & Deng, W. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.016 · Cited by 30
“Around 500,000 hip and knee joint replacements necessitated by OA are performed annually in the US and this might be doubled by 2015 [2].”
Background
MicroRNA-17-5p contributes to osteoarthritis progression by binding p62/SQSTM1
Li, H., Miao, D., Zhu, Q., Huang, J., Lu, G., & Xu, W. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5622 · Cited by 29
Retracted
Autophagy: a new therapeutic target in cartilage injury and osteoarthritis.
Lotz, M., & Caramés, B. (2012) · Journal of the American Academy of Orthopaedic Surgeons · doi:10.5435/jaaos-20-04-261 · Cited by 31
“By contrast, inhibiting the failure of a critical cellular homeostasis mechanism, such as autophagy, leads to global changes in gene expression and can ultimately cause cell death and extracellular matrix destruction,(2) two main features of OA-affected cartilage.(11) The in vitro and in vivo studies of rapamyMartin L…”
Background
Identification of the osteoarthritis signature gene PDK1 by machine learning and its regulatory mechanisms on chondrocyte autophagy and apoptosis
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“Increasing evidence has shown that OA progression occurs along with autophagy attenuation in cells (7).”
Background
Defective chaperone-mediated autophagy is a hallmark of joint disease in patients with knee osteoarthritis
Lorenzo-Gómez, I., Nogueira-Recalde, U., Garcia-Dominguez, C., Oreiro-Villar, N., Lotz, M., Pinto-Tasende, J., Blanco, F. J., & Caramés, B. (2023) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2023.02.076 · Cited by 29
Applications of Proteomics to Osteoarthritis, a Musculoskeletal Disease Characterized by Aging
Mobasheri, A. (2011) · Frontiers in Physiology · doi:10.3389/fphys.2011.00108 · Cited by 29
“AGING AND OSTEOARTHRITIS Aging is a major contributor to musculoskeletal degeneration and the development of OA (Hamerman, 1998; Lotz and Carames, 2011).”
Background
A new frontier in temporomandibular joint osteoarthritis treatment: Exosome-based therapeutic strategy
Yuan, W., Wu, Y., Huang, M., Zhou, X., Liu, J., Yi, Y., Wang, J., & Liu, J. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1074536 · Cited by 29
Tougu Xiaotong capsule inhibits the tidemark replication and cartilage degradation of papain-induced osteoarthritis by the regulation of chondrocyte autophagy
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Collagen-based hydrogels induce hyaline cartilage regeneration by immunomodulation and homeostasis maintenance
Gao, Y., Wang, J., Dai, W., Li, S., Liu, Q., Zhao, X., Fu, W., Xiao, Y., Guo, L., Fan, Y., et al. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.07.018 · Cited by 27
C10orf10/DEPP activates mitochondrial autophagy and maintains chondrocyte viability in the pathogenesis of osteoarthritis
Kuwahara, M., Akasaki, Y., Kurakazu, I., Sueishi, T., Toya, M., Uchida, T., Tsutsui, T., Hirose, R., Tsushima, H., Teramura, T., et al. (2022) · The FASEB Journal · doi:10.1096/fj.202100896r · Cited by 25
CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis
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“Increased reactive oxygen species (ROS) and decreased antioxidants result in increased oxidative stress and thus the activation of various catabolic factors, including extracellular matrix (ECM)-degrading proteases 11 .”
Down-regulation of protease-activated receptor 2 ameliorated osteoarthritis in rats through regulation of MAPK/NF-κB signaling pathwayin vivoandin vitro
Yan, S., Ding, H., Junyang, P., Wang, X., Pang, C., Wei, J., Wei, J., & Chen, H. (2020) · Bioscience Reports · doi:10.1042/bsr20192620 · Cited by 25
Icariin protects rabbit BMSCs against OGD-induced apoptosis by inhibiting ERs-mediated autophagy via MAPK signaling pathway
Liu, D., Tang, W., Zhang, H., Huang, H., Zhang, Z., Tang, D., & Jiao, F. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117730 · Cited by 25
Novel perspectives on leptin in osteoarthritis: Focus on aging
Liu, Z., Xie, W., Li, H., Liu, X., Lu, Y., Lu, B., Deng, Z., & Li, Y. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.101159 · Cited by 30
“Hence, autophagy guarantees cell survival at a basal level by immediately eliminating falsely folded proteins and facilitating organelle turnover, 159 endoplasmic reticulum stress response, and normal protein functions.”
Background
Retracted : GABARAP promotes bone marrow mesenchymal stem cells‐based the osteoarthritis cartilage regeneration through the inhibition of PI3K/AKT/mTOR signaling pathway
Wu, Z., Lu, H., Yao, J., Zhang, X., Huang, Y., Ma, S., Zou, K., Wei, Y., Yang, Z., Li, J., et al. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28705 · Cited by 24
“Studies show that autophagy inhibits apoptosis and cartilage metabolism disorder caused by inflammation and aging (Lotz & Caramés, 2011).”
Background
Retracted
Polyamine delivery as a tool to modulate stem cell differentiation in skeletal tissue engineering
Borzı̀, R. M., Guidotti, S., Minguzzi, M., Facchini, A., Platano, D., Trisolino, G., Filardo, G., Cetrullo, S., D’Adamo, S., Stefanelli, C., et al. (2013) · Amino Acids · doi:10.1007/s00726-013-1607-9 · Cited by 24
“Conflict of interest The authors declare that they have no conflict of interest.”
Background
Genetic association, mRNA and protein expression analysis identify ATG4C as a susceptibility gene for Kashin–Beck disease
Wu, C., Wen, Y., Guo, X., Yang, T., Shen, H., Chen, X., Tian, Q., Tan, L., Deng, H., & Zhang, F. (2016) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2016.09.019 · Cited by 24
“Dysfunction of autophagy is an important mechanism for damage accumulation and aging of articular cartilage in osteoarthritis (OA) [12].”
Background
Programmed Cell Death of Chondrocytes, Synovial Cells, Osteoclasts, and Subchondral Bone Cells in Osteoarthritis
Huang, J., Wu, L., Zhao, Y., & Zhao, H. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s514309 · Cited by 28
“212 Nonetheless, research on the impact of excessive autophagy on cartilage or chondrocyte function remains scarce.”
Defective autophagy activity and its association with spinal damage in patients with ankylosing spondylitis
Park, M., Kim, H. W., Lee, S., Song, J. J., & Park, Y. (2016) · Joint Bone Spine · doi:10.1016/j.jbspin.2016.09.005 · Cited by 24
OPN inhibits autophagy through CD44, integrin and the MAPK pathway in osteoarthritic chondrocytes
Bai, R., Liu, D., Li, Y., Tian, J., Yu, D., Li, H.-Z., & Zhang, F. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.919366 · Cited by 23
“The occurrence and development of aging-related diseases are closely related to defects in autophagy, and recent studies have shown that this process is relevant to the damage and degeneration of chondrocytes (9).”
Background
Dietary Fats and Osteoarthritis: Insights, Evidences, and New Horizons
Sekar, S., Crawford, R., Xiao, Y., & Prasadam, I. (2016) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25758 · Cited by 24
PLCγ1 inhibition‐driven autophagy of IL‐1β‐treated chondrocyte confers cartilage protection against osteoarthritis, involving AMPK, Erk and Akt
Chen, X., Wang, Y., Qu, N., Zhang, B., & Xia, C. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16245 · Cited by 22
Chondrogenic Differentiation of Amniotic Fluid Stem Cells and Their Potential for Regenerative Therapy
Preitschopf, A., Zwickl, H., Li, K., Lübec, G., Joó, G. J., Rosner, M., Hengstschläger, M., & Mikula, M. (2012) · Stem Cell Reviews and Reports · doi:10.1007/s12015-012-9405-4 · Cited by 22
“In articular cartilage autophagy plays an important role, since it protects chondrocytes from age related cell death and preserves homeostasis within the tissue [81].”
Background
Targeting the senescence-related genes MAPK12 and FOS to alleviate osteoarthritis
Geng, N., Xian, M., Deng, L., Kuang, B., Pan, Y., Liu, K., Ye, Y., Fan, M., Bai, Z., & Guo, F. (2024) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2024.06.008 · Cited by 22
“The number of individual articular chondrocytes in adulthood is stable and hardly increase, so chondrocytes are more susceptible to external stimuli such as ultraviolet radiation, oxidative damage and chronic inflammation, which will induce cellular senescence of chondrocytes [28].”
Background
Autophagy guards tendon homeostasis
Montagna, C., Svensson, R. B., Bayer, M. L., Rizza, S., Maiani, E., Yeung, C. C., Filomeni, G., & Kjær, M. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04824-7 · Cited by 22
“Notably, among other connective tissues, cartilage has been extensively reported to be regulated by autophagy [34, 35].”
変形性関節症において、C10orf10/DEPPはミトコンドリアオートファジーを活性化し、軟骨細胞の生存を維持する
桑原, 正. (2022) · Kyushu University Institutional Repository (QIR) (Kyushu University) · Cited by 21
Activation of autophagy contributes to the protective effects of lycopene against oxidative stress‐induced apoptosis in rat chondrocytes
Wu, Z., Zhang, X., Li, Z., Wen, Z., & Lin, Y.-C. (2021) · Phytotherapy Research · doi:10.1002/ptr.7127 · Cited by 20
“…in maintaining intracellular homeostasis and recycling broken organelle (Levine & Kroemer, 2008; Mizushima, Levine, Cuervo, & Klionsky, 2008), and has a role in OA progression and oxidative injury of chondrocytes (Goutas, Syrrou, Papathanasiou, Tsezou, & Trachana, 2018; Lotz & Caramés, 2011).”
Background
Emerging therapeutic targets for osteoarthritis
Hadzic, E., & Beier, F. (2023) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2023.2185133 · Cited by 20
“Articular chondrocytes are characterized by very low cell division, and so autophagy is required to maintain cartilage homeostasis [14].”
Background
LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis
Guan, M., Han, X., Liao, B., Han, W., Chen, L., Zhang, B., Peng, X., Tian, Y., Xiao, G., Li, X., et al. (2025) · Advanced Science · doi:10.1002/advs.202413930 · Cited by 19
CF101 alleviates OA progression and inhibits the inflammatory process via the AMP/ATP/AMPK/mTOR axis
Liu, L., Bai, H., Jiao, G., Wang, X., Zhang, Z., Song, X., Ma, T., Li, T., & Gao, L. (2021) · Bone · doi:10.1016/j.bone.2021.116264 · Cited by 19
High TRB3 expression induces chondrocyte autophagy and senescence in osteoarthritis cartilage
Gu, Y., Ren, Y., Wang, Y., Zeng, Y., & Yao, Q. (2022) · Aging · doi:10.18632/aging.204066 · Cited by 20
Autophagy attenuates osteoarthritis in mice by inhibiting chondrocyte pyroptosis and improving subchondral bone remodeling
Yan, J., Feng, G., Yang, Y., Ding, D., Ma, L., Zhao, X. S., Chen, X., Wang, H., Chen, Z., & Jin, Q. (2022) · Biomolecules and Biomedicine · doi:10.17305/bjbms.2022.7677 · Cited by 20
“Meanwhile, LC3 is a structural and functional molecule formed by autophagy, and its expression level reflects the level of autophagy activation [49, 50]; LC3 is significantly downregulated in OA [51].”
Background
DDIT3 aggravates TMJOA cartilage degradation via Nrf2/HO-1/NLRP3-mediated autophagy
Yang, C., Dong, W., Wang, Y., Dong, X., Xu, X., Yu, X., & Wang, J. (2024) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2024.04.017 · Cited by 19
Therapeutic Controlled Release Strategies for Human Osteoarthritis
Wang, D., Liu, W., Venkatesan, J., Madry, H., & Cucchiarini, M. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202402737 · Cited by 24
Altered swelling and ion fluxes in articular cartilage as a biomarker in osteoarthritis and joint immobilization: a computational analysis
Manzano, S., Manzano, R., Doblaré, M., & Doweidar, M. H. (2014) · Journal of The Royal Society Interface · doi:10.1098/rsif.2014.1090 · Cited by 19
“This has recently been confirmed experimentally [2,56], and associated with weakening of the collagen network and subsequent reduction of PG content.”
Gelatin reduced Graphene Oxide Nanosheets as Kartogenin Nanocarrier Induces Rat ADSCs Chondrogenic Differentiation Combining with Autophagy Modification
Jiao, D., Wang, J., Yu, W., Zhang, N., Zhang, K., & Bai, Y. (2021) · Materials · doi:10.3390/ma14051053 · Cited by 18
“Autophagy as the cellular homeostasis mechanism could remove the dysfunctional organelles and macromolecules, and recent observations illustrate that the pathogenesis of the aging-related diseases, including OA, usually involves the change of compromised or defective autophagy [24].”
Background
Bioinformatics analysis combined with experimental validation to explore the mechanism of XianLing GuBao capsule against osteoarthritis
Xiao, J., Zhang, G., Mai, J., He, Q., Chen, W., Li, J., Ma, Y., Pan, Z., Yang, J., Li, S., et al. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115292 · Cited by 18
Methyl gallate prevents oxidative stress induced apoptosis and ECM degradation in chondrocytes via restoring Sirt3 mediated autophagy and ameliorates osteoarthritis progression
Li, Y., Shen, B., Lv, C., Zhu, X., Naren, Q., Xu, D., Chen, H., & Wu, F. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109489 · Cited by 18
Zyxin‐involved actin regulation is essential in the maintenance of vinculin focal adhesion and chondrocyte differentiation status
Li, G., Song, X., Li, R., Sun, L., Gong, X., Chen, C., & Yang, L. (2018) · Cell Proliferation · doi:10.1111/cpr.12532 · Cited by 18
Punicalagin Inhibits Tert-Butyl Hydroperoxide-Induced Apoptosis and Extracellular Matrix Degradation in Chondrocytes by Activating Autophagy and Ameliorates Murine Osteoarthritis
Jinsong, K., Wang, J., Gong, X., Zheng, X. M., & Chen, T. (2020) · Drug Design Development and Therapy · doi:10.2147/dddt.s282932 · Cited by 18
Emerging pharmaceutical therapeutics and delivery technologies for osteoarthritis therapy
Shentu, C., Yan, G., Xu, D.-C., Chen, Y., & Peng, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.945876 · Cited by 18
“Another important aspect is the determination of the best mass ratio of each agent within a co-deliver drugs system which needs a systematic study to investigate the effects of different drug ratios on biological efficacy (Karsdal et al., 2016; Lotz and Caramés, 2011; Hunter, 2011; Vos et al., 2012).”
Background
Non-apoptotic cell death in osteoarthritis: Recent advances and future
Ji, P., Zhou, Z., Zhang, J., Bai, T., Li, C., Zhou, B., Wang, M., Tan, Y., & Wang, S. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117344 · Cited by 17
Oxidative stress-induced DNA damage and repair in primary human osteoarthritis chondrocytes: focus on IKKα and the DNA Mismatch Repair System
Neri, S., Guidotti, S., Bini, C., Pelotti, S., D’Adamo, S., Minguzzi, M., Platano, D., Santi, S., Mariani, E., Cattini, L., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.02.020 · Cited by 17
Inhibition of mammalian target of rapamycin complex 1 signaling by n-3 polyunsaturated fatty acids promotes locomotor recovery after spinal cord injury
Nie, J., Chen, J., Yang, J., Pei, Q., Li, J., Liu, J. S., Xu, L., Li, N., Chen, Y., Chen, X., et al. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8583 · Cited by 16
“Studies have shown that inhibiting mTORC1 can enhance autophagy and help repair injuries (13,28-37).”
Background
Sirtuins in osteoarthritis: current understanding
Liu, Y., Zhang, Z., Liu, C., & Zhang, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1140653 · Cited by 18
“Several autophagyrelated proteins, such as ATG5, LC3A, ULK1, BECN and LC3, have been reported to be decreased with increased age or in an OA mouse model (78, 79).”
Background
Propolis Reduces the Expression of Autophagy-Related Proteins in Chondrocytes under Interleukin-1β Stimulus
Arias, C., Saavedra, N., Saavedra, K., Marysol Alvear, Z., Cuevas, A., Maria–Engler, S. S., Abdalla, D. S. P., & Salazar, L. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153768 · Cited by 16
“Currently, there are no drugs available to modify OA and a large number of candidate drugs have failed to demonstrate efficacy or they were associated with significant side effects [23,42].”
Background
Comorbidity phenotypes and risk of mortality in patients with osteoarthritis in the UK: a latent class analysis
Zemedikun, D. T., Lee, H., Nirantharakumar, K., Raza, K., Chandan, J. S., Lord, J. M., & Jackson, T. (2022) · Arthritis Research & Therapy · doi:10.1186/s13075-022-02909-4 · Cited by 19
“It is now recognised that hallmarks of ageing contribute to abnormal cartilage homeostasis [41, 56, 57].”
Background
Recombinant human irisin regulated collagen II, matrix metalloproteinase‑13 and the Wnt/β‑catenin and NF‑κB signaling pathways in interleukin‑1β‑induced human SW1353 cells
Li, X., Liu, Y., Liu, Q., Wang, S., Ma, Y., & Jin, Q. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8562 · Cited by 15
“β-catenin is a key factor in the Wnt/β-catenin signaling pathway and its expression level in the nucleus directly reflects the activation level of this signaling pathway (11).”
Background
Thermosensitive injectable hydrogel loaded with hypoxia-induced exosomes maintains chondrocyte phenotype through NDRG3-mediated hypoxic response
Song, X., Gu, L., Yang, Q., Wu, J., Chen, J., Tian, X., Sun, L., & Chen, L. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.108079 · Cited by 14
Restriction of spontaneous and prednisolone-induced leptin production to dedifferentiated state in human hip OA chondrocytes: role of Smad1 and β-catenin activation
Charlier, E., Malaise, O., Zeddou, M., Neuville, S., Cobraiville, G., Deroyer, C., Sanchez, C., Gillet, P., Kurth, W., de Seny, D., et al. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.08.002 · Cited by 14
Drying of open animal joints in vivo subsequently causes cartilage degeneration
Paterson, S. I., Eltawil, N. M., Simpson, H., Amin, A. K., & Hall, A. C. (2016) · Bone and Joint Research · doi:10.1302/2046-3758.54.2000594 · Cited by 14
Progranulin regulation of autophagy contributes to its chondroprotective effect in osteoarthritis
Pan, Y., Yang, Y., Fan, M., Chen, C., Jiang, R., Li, L., Xian, M., Kuang, B., Geng, N., Feng, N., et al. (2022) · Genes & Diseases · doi:10.1016/j.gendis.2022.05.031 · Cited by 14
“Many studies have reported the constitutive activation of autophagy, thus regarding it as a protective or homeostatic mechanism of normal cartilage.(5,7,8) Autophagy is involved in the pathogenesis of OA through the modulation of chondrocyte homeostasis.”
Background
Pathogenesis of Osteoarthritis
Kapoor, M. (2015) · Springer eBooks · doi:10.1007/978-3-319-19560-5_1 · Cited by 17
Senile Osteoarthritis Regulated by the Gut Microbiota: From Mechanisms to Treatments
Yu, F., Zhu, C., & Wu, W. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041505 · Cited by 14
“…cells in senescent tissues decreases, and the clearance efficiency decreases, leading to increased aggregation of various macromolecular proteins [93], which attenuates the protective effect on cartilage and ultimately results in cartilage degeneration and a series of aging-related diseases [94].”
Artificial osteochondral interface of bioactive fibrous membranes mediating calcified cartilage reconstruction
Liu, M., Ke, X., Yao, Y., Wu, F., Ye, S., Zhang, L., Yang, G., Shen, M., Li, Y., Yang, X., et al. (2021) · Journal of Materials Chemistry B · doi:10.1039/d1tb01238j · Cited by 13
Modulating Autophagy in Osteoarthritis: Exploring Emerging Therapeutic Drug Targets
Andrei, C., Mihai, D. P., Nițulescu, G. M., Nițulescu, G., & Zanfirescu, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413695 · Cited by 15
Local intra-articular injection of rapamycin inhibits NLRP3 activity and prevents osteoarthritis in mouse DMM models
Xu, G., Wang, J., Ma, L., Zhao, X. S., Luo, W., & Jin, Q. (2019) · Autoimmunity · doi:10.1080/08916934.2019.1643844 · Cited by 13
“Autophagy-related T-regulatory factors (LC3, Atg5) have been shown to be down regulated in OA [42], consistent with this study.”
Result
CircCDK14 ameliorates interleukin-1β-induced chondrocyte damage by the miR-1183/KLF5 pathway in osteoarthritis
Lai, X., Song, Y., & Tian, J. (2022) · Autoimmunity · doi:10.1080/08916934.2022.2081843 · Cited by 13
RETRACTED ARTICLE: Chondro-protective effects of polydatin in osteoarthritis through its effect on restoring dysregulated autophagy via modulating MAPK, and PI3K/Akt signaling pathways
Wu, Z., Luan, Z., Zhang, X., Zou, K., Ma, S., Yang, Z., Feng, W., He, M., Jiang, L., Li, J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50471-y · Cited by 13
Retracted
Age-dependent differences in response to partial-thickness cartilage defects in a rat model as a measure to evaluate the efficacy of interventions for cartilage repair
Akatsu, Y., Enomoto, T., Yamaguchi, S., Tahara, M., Fukawa, T., Endo, J., Hoshi, H., Yamamoto, Y., Sasaki, T., Takahashi, K., et al. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2914-y · Cited by 12
mtDNA variability determines spontaneous joint aging damage in a conplastic mouse model
Scotece, M., Vaamonde‐García, C., Lechuga‐Vieco, A. V., Cortés, A. C., Jiménez-Gómez, M. C., Filgueira-Fernández, P., Rego‐Pérez, I., Enrı́quez, J. A., & Blanco, F. J. (2022) · Aging · doi:10.18632/aging.204153 · Cited by 14
“In association with other risk factors, such as obesity, mechanical injury, and genetics, these aging-related changes may lead to an earlier onset or the development of a more severe form of osteoarthritis (OA) [2].”
BackgroundInfluential
Ozone induces autophagy by activating PPARγ/mTOR in rat chondrocytes treated with IL-1β
Sun, P., Xu, W., Zhao, X., Zhang, C., Lin, X., Gong, M., & Fu, Z. (2022) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-022-03233-y · Cited by 13
“Previous reports have demonstrated that autophagy may be constitutively activated in normal chondrocytes and defective autophagy in chondrocytes is associated with the degradation of cartilage and the development of OA [36, 37].”
Background

Authors: Lotz, M. K., & Caramés, B.
Affiliations: Scripps Research Institute (US)
Corresponding author: Lotz, Martin K.
ORCID: Lotz, Martin K.
Caramés, Beatriz
Venue: Nature Reviews Rheumatology
Publisher: Springer Science and Business Media LLC
Published: 2011-08-02
Volume: 7
Issue: 10
Pages: 579-587
ISSN: 1759-4790 (ISSN-L)
1759-4804
DOI: 10.1038/nrrheum.2011.109
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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Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA

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