Associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage enzymes in patients with knee osteoarthritis

Ruan, Guangfeng; Xu, Jianhua; Wang, K.; Zheng, Shuang; Wu, Juan; Ren, Jiale; Bian, Fuqin; Chang, Bingru; Zhu, Zhaohua; Han, Weiyu; Ding, Changhai

doi:10.1016/j.joca.2018.08.020

Cited by 27 publications

(22 citation statements)

References 33 publications

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“…Ruan et al showed that levels of serum matrix metalloproteinase (MMP, an enzyme involved in type II collagen degradation) was positively associated with KL grade on Xrays and infrapatellar fat pad signal intensity and medial femur cartilage defects on MRI and was negatively associated with patellar cartilage volume and infrapatellar fat pad volume on MRI 61 . Another study by Ruan et al showed that levels of serum S100A8 and S100A9 (enzymes involved in cartilage degeneration) were positively associated with WOMAC score, cartilage defects on MRI, and serum MMP levels 62 . Joseph et al investigated the association between MRI findings and levels of serum MMP, serum hyaluron (HA, an enzyme involved in osteophyte formation and synovitis), serum cartilage oligomeric matrix protein (COMP, an enzyme involved in cartilage degeneration), and urine carboxy-terminal telopeptides of type II collagen (CTX-II, an enzyme involved in type II collagen degradation).…”

Section: Imaging Findings and Serum And Urine Biomarkers In Knee Oamentioning

confidence: 99%

Osteoarthritis year in review 2019: imaging

Kijowski

Demehri

Roemer

et al. 2020

Osteoarthritis and Cartilage

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PET-MRI". Articles were reviewed to determine relevance based upon the following criteria: 1) study involved human subjects with OA or risk factors for OA and 2) study involved imaging to evaluate OA disease status or OA treatment response. Relevant articles were ranked according to scientific merit, with the best publications selected for inclusion in the narrative report. Results: The PubMed search revealed a total of 1257 articles, of which 256 (20.4%) were considered relevant to OA imaging. Two-hundred twenty-six (87.1%) articles involved the knee joint, while 195 (76.2%) articles involved the use of magnetic resonance imaging (MRI). The proportion of published studies involving the use of MRI was higher than previous years. An increasing number of articles were also published on imaging of subjects with joint injury and on deep learning application in OA imaging. Conclusion: MRI and other imaging modalities continue to play an important role in research studies designed to better understand the pathogenesis, progression, and treatment of OA.

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Section: Imaging Findings and Serum And Urine Biomarkers In Knee Oamentioning

confidence: 99%

Osteoarthritis year in review 2019: imaging

Kijowski

Demehri

Roemer

et al. 2020

Osteoarthritis and Cartilage

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“…1) Ampd1 (encodes adenosine monophosphate deaminase 1): Patients with Ampd1 deficiency experience muscle pain (myalgia) or weakness after exercise; 32 2) S100a8 (encodes S100 calciumbinding protein A8): the S100a8 protein is positively associated with increased knee symptoms, cartilage defects in patients with knee osteoarthritis. 33 In addition, KEGG pathway analysis for the DE mRNAs indicates some potential targets, such as inflammatory mediator-regulated transient…”

Section: Discussionmentioning

confidence: 99%

<p>Transcriptome Analysis of Dorsal Root Ganglion in Rats with Knee Joint Inflammation</p>

Bai

Cao

Dong

et al. 2020

JPR

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Background Rheumatoid arthritis (RA) leads to pain through alteration of gene expression. Although gene expression alteration in knee cartilage or peripheral blood from RA patients has been identified using microarray, it remains unclear whether long non-coding RNA (lncRNA)-mediated gene regulation occurs in primary sensory neurons of dorsal root ganglia (DRG) during RA-like joint inflammation. In the present study, we aimed to analyze lncRNA and related mRNA profiles in the DRG in a knee joint inflammation rat model. Methods Complete Freund’s adjuvant (CFA) was injected in the rat knee joint for preparing the joint inflammation model. A lncRNA-mRNA microarray of rat DRG was employed for transcriptome analysis. Functional roles of differentially expressed lncRNAs and their related mRNAs in the injured DRG were delineated by bioinformatic analysis. Results We observed that expression levels of 9000 lncRNAs were altered on day 7 post-CFA, of which 45.17% were up-regulated and 54.83% were down-regulated. Specifically, 69 lncRNAs (42 up and 27 down) were significantly regulated. We also observed that expression levels of 13,744 mRNAs were altered on day 7 post-CFA, of which 49.67% were up-regulated and 50.33% were down-regulated. Specifically, 102 mRNAs (51 up and 51 down) were significantly regulated. Using quantitative real-time PCR, we verified the changes in differentially expressed lncRNAs in the injured DRG. Conclusion These results suggest that microarray-based RNA sequencing can be used to identify altered lncRNAs and relevant mRNAs in the DRG of rats with knee joint inflammation.

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“…Our findings are consistent with other recent studies demonstrating a role for MMP-13 in the progression of arthritis. 45 MMPs and their endogenous inhibitors play a critical role in maintaining the dynamic homeostasis and integrity of the extracellular matrix. 6 Previous studies reported that articular chondrocytes from OA knees, rather than normal knees, could express MMP-13.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase Inhibition With Doxycycline Affects the Progression of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Rupture: Evaluation in a New Nonsurgical Murine ACL Rupture Model

et al. 2019

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Background: Doxycycline has broad-spectrum activity as a matrix metalloproteinase (MMP) inhibitor and thus could reduce the progression of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) rupture. Hypothesis: Doxycycline would inhibit progression of PTOA in a murine ACL rupture model. Study Design: Controlled laboratory study. Methods: For the in vitro study, cadaveric C57BL/6 male mice knees (N = 108) were used for the development of a nonsurgical ACL rupture model. For the in vivo study, 24 C57BL/6 male mice then underwent ACL rupture with our manual procedure and were divided into 4 groups: untreated control; doxycycline, 10 mg/kg/d; doxycycline, 50 mg/kg/d; and doxycycline, 100 mg/kg/d. Doxycycline was administered in drinking water beginning immediately after ACL rupture. Radiographic imaging and paw prints were evaluated at 3, 7, 14, and 28 days. The foot length and toe spread were analyzed as measures of function. Histology and MMP-13 immunohistochemistry were done at 4 weeks. Results: Radiographs demonstrated anterior tibial subluxation and meniscal extrusion after ACL rupture, confirming knee joint instability without fractures. Statistically significant differences in gait were found between the intact and experimental groups. Histologic examination demonstrated cartilage damage, meniscal tears, and mild osteoarthritis after ACL rupture, similar to what occurs in human patients. Hypertrophy of the posterior horn of the medial and lateral meniscus was found, and tears of the posterior horn of the menisci were common. All doxycycline groups had a lower score than the untreated control group, indicating less cartilage damage. The posterior tibia of the untreated group had the most cartilage damage as compared with the 3 doxycycline groups, with a significant difference between the untreated and 50-mg/kg/d doxycycline groups, suggesting that the latter dose may protect against proteoglycan loss and decrease the progression of osteoarthritis. The nondoxycycline group had the highest synovial inflammation score among all groups, indicating that doxycycline has an inhibitory effect on synovitis. There was significantly lower MMP-13 expression on the tibia in the doxycycline-treated groups, with a positive correlation between doxycycline concentration and MMP-13 inhibition. Conclusion: Modulation of MMP-13 activity by doxycycline treatment may offer a novel biological pathway to decrease the progression of PTOA after ACL rupture. Clinical Relevance: Doxycycline is an approved, readily available drug with infrequent side effects of photosensitivity and gastrointestinal symptoms. Future clinical trials could evaluate doxycycline to reduce or prevent progressive cartilage damage after ACL rupture.

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Associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage enzymes in patients with knee osteoarthritis

Cited by 27 publications

References 33 publications

Osteoarthritis year in review 2019: imaging

Osteoarthritis year in review 2019: imaging

<p>Transcriptome Analysis of Dorsal Root Ganglion in Rats with Knee Joint Inflammation</p>

Matrix Metalloproteinase Inhibition With Doxycycline Affects the Progression of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Rupture: Evaluation in a New Nonsurgical Murine ACL Rupture Model

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