The regulation of cartilage extracellular matrix homeostasis in joint cartilage degeneration and regeneration

Peng, Zhi; Sun, Heng; Bunpetch, Varitsara; Koh, Yi Wen; Wen, Ya; Wu, Dongmei; Ouyang, Hongwei

doi:10.1016/j.biomaterials.2020.120555

Cited by 194 publications

(127 citation statements)

References 78 publications

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“…In healthy cartilage, the ECM was kept in a slow, continuous state of turnover, often described as homeostasis. When the ECM was in homeostasis, overall anabolic and catabolic activities of matrix synthesis and degradation were in balance ( Rahmati et al, 2017 ; Guilak et al, 2018 ; Krishnan and Grodzinsky, 2018 ; Peng et al, 2020 ). However, the homeostasis of ECM was disrupted during the development of OA, characterized by the increase of catabolic activities, caused the gradual degeneration of cartilage ( Guilak et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Ling

Zeng

et al. 2021

Front. Pharmacol.

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Osteoarthritis (OA) is a common disease characterized by cartilage degeneration. In recent years much attention has been paid to Traditional Chinese Medicine (TCM) since its treatments have shown efficacy for ameliorating cartilage degradation with mild side effects. Osteoking is a TCM prescription that has long been used in OA treatment. However, the exact mechanism of Osteoking are not fully elucidated. In the current study, destabilization of the medial meniscus (DMM)-induced OA mice was introduced as a wild type animal model. After 8 weeks of administration of Osteoking, histomorphometry, OARSI scoring, gait analysis, micro-CT, and immunohistochemical staining for Col2, MMP-13, TGFβRII and pSmad-2 were conducted to evaluate the chondroprotective effects of Osteoking in vivo. Further in vitro experiments were then performed to detect the effect of Osteoking on chondrocytes. TGFβRIICol2ER transgenic mice were constructed and introduced in the current study to validate whether Osteoking exerts its anti-OA effects via the TGF-β signaling pathway. Results demonstrated that in wild type DMM mice, Osteoking ameliorated OA-phenotype including cartilage degradation, subchondral bone sclerosis, and gait abnormality. Col2, TGFβRII, and pSmad-2 expressions were also found to be up-regulated after Osteoking treatment, while MMP-13 was down-regulated. In vitro, the mRNA expression of MMP-13 and ADAMTS5 decreased and the mRNA expression of Aggrecan, COL2, and TGFβRII were up-regulated after the treatment of Osteoking in IL-1β treated chondrocytes. The additional treatment of SB505124 counteracted the positive impact of Osteoking on primary chondrocytes. In TGFβRIICol2ER mice, spontaneous OA-liked phenotype was observed and treatment of Osteoking failed to reverse the OA spontaneous progression. In conclusion, Osteoking ameliorates OA progression by decelerating cartilage degradation and alleviating subchondral bone sclerosis partly via the TGF-β signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Ling

Zeng

et al. 2021

Front. Pharmacol.

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“…Osteoarthritis (OA) has often been described as a degenerative joint disorder where the articular cartilage breaks down as a result of wear and tear, causing the bones to rub against each other, producing pain. However, OA is better defined as a whole joint disease that also affects subchondral bone, synovial membrane, ligaments and menisci (Loeser et al, 2012;Peng et al, 2021). Development of OA involves abnormal behavior of chondrocytes and altered metabolic homeostasis of the cartilage extracellular matrix.…”

Section: Oscar Expression In Chondrocytes: a Link To Osteoarthritismentioning

confidence: 99%

“…Development of OA involves abnormal behavior of chondrocytes and altered metabolic homeostasis of the cartilage extracellular matrix. These result in chronic inflammation and defective remodeling of articular cartilage and neighboring bone driven by matrix degrading enzymes and inflammatory cytokines (Kapoor et al, 2011;Loeser et al, 2012;Hu and Ecker, 2021;Peng et al, 2021).…”

Section: Oscar Expression In Chondrocytes: a Link To Osteoarthritismentioning

confidence: 99%

Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

Nedeva

Vitale

Elson

et al. 2021

Front. Cell Dev. Biol.

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Formation of mature bone-resorbing cells through osteoclastogenesis is required for the continuous remodeling and repair of bone tissue. In aging and disease this process may become aberrant, resulting in excessive bone degradation and fragility fractures. Interaction of receptor-activator of nuclear factor-κB (RANK) with its ligand RANKL activates the main signaling pathway for osteoclastogenesis. However, compelling evidence indicates that this pathway may not be sufficient for the production of mature osteoclast cells and that co-stimulatory signals may be required for both the expression of osteoclast-specific genes and the activation of osteoclasts. Osteoclast-associated receptor (OSCAR), a regulator of osteoclast differentiation, provides one such co-stimulatory pathway. This review summarizes our present knowledge of osteoclastogenesis signaling and the role of OSCAR in the normal production of bone-resorbing cells and in bone disease. Understanding the signaling mechanism through this receptor and how it contributes to the production of mature osteoclasts may offer a more specific and targeted approach for pharmacological intervention against pathological bone resorption.

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“…Integral ECM is essential to the normal load-bearing function of articular cartilage. Moreover, the ECM regulates most cellular behaviors and is necessary for major developmental processes 4 . However, in OA, a number of matrix-degrading enzymes, including matrix metalloproteinases (MMPs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTS) are significantly upregulated, which accelerates the remodeling and loss of flexibility of the ECM even before cartilage destruction occurs 5 .…”

Section: Introductionmentioning

confidence: 99%

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway

Liu

Pan

et al. 2021

Cell Death Dis

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Milk fat globule-epidermal growth factor (EGF) factor 8 (MFG-E8), as a necessary bridging molecule between apoptotic cells and phagocytic cells, has been widely studied in various organs and diseases, while the effect of MFG-E8 in osteoarthritis (OA) remains unclear. Here, we identified MFG-E8 as a key factor mediating chondrocyte senescence and macrophage polarization and revealed its role in the pathology of OA. We found that MFG-E8 expression was downregulated both locally and systemically as OA advanced in patients with OA and in mice after destabilization of the medial meniscus surgery (DMM) to induce OA. MFG-E8 loss caused striking progressive articular cartilage damage, synovial hyperplasia, and massive osteophyte formation in OA mice, which was relieved by intra-articular administration of recombinant mouse MFG-E8 (rmMFG-E8). Moreover, MFG-E8 restored chondrocyte homeostasis, deferred chondrocyte senescence and reprogrammed macrophages to the M2 subtype to alleviate OA. Further studies showed that MFG-E8 was inhibited by miR-99b-5p, expression of which was significantly upregulated in OA cartilage, leading to exacerbation of experimental OA partially through activation of NF-κB signaling in chondrocytes. Our findings established an essential role of MFG-E8 in chondrocyte senescence and macrophage reprogramming during OA, and identified intra-articular injection of MFG-E8 as a potential therapeutic target for OA prevention and treatment.

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The regulation of cartilage extracellular matrix homeostasis in joint cartilage degeneration and regeneration

Cited by 194 publications

References 78 publications

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Osteoking Decelerates Cartilage Degeneration in DMM-Induced Osteoarthritic Mice Model Through TGF-β/smad-dependent Manner

Role of OSCAR Signaling in Osteoclastogenesis and Bone Disease

MFG-E8 regulated by miR-99b-5p protects against osteoarthritis by targeting chondrocyte senescence and macrophage reprogramming via the NF-κB pathway

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