Skip to main content

Elevation of MMP1 and ADAMTS5 mRNA expression in glenohumeral synovia of patients with hypercholesterolemia

Abstract

Background

Epidemiological studies have reported a positive association between hypercholesterolemia and shoulder disease. Previous studies have focused on the effect of hypercholesterolemia on tendinopathy. Moreover, hypercholesterolemia has also been linked to joint pathology in the knee and hand. However, the effect of hyperlipidemia on glenohumeral joint remain unclear. A hypercholesterolemic condition has been reported to alter levels of A Disintegrin and Metalloprotease with Thrombospondin Motifs (ADAMTSs) and matrix metalloproteases (MMPs) in synovium of the knee joint. Here, we evaluated the mRNA expression of ADAMTSs and MMPs in the glenohumeral synovium of patients with and without hypercholesterolemia.

Methods

Study participants were 73 patients who underwent arthroscopic rotator cuff repair for degenerative rotator cuff tears. They were divided into two groups according to total cholesterol (TC) and triglyceride levels. Synovial membrane samples were harvested at the rotator interval during surgery, and mRNA expression levels of the aggrecanases ADAM-TS4 and ADAM-TS5 and MMPs (MMP-1, 3, 9, and 13) were analyzed quantitatively.

Results

ADAM-TS5 and MMP1 mRNA levels were significantly higher in the high TC group than in the low TC group (P = 0.023 and P = 0.025, respectively). In contrast, no significant differences were observed in ADAMTS4 or MMPs 3, 9, and 13 (ADAMTS4, P = 0.547; MMP3, P = 0.55; MMP9, P = 0.521; and MMP13, P = 0.785).

Conclusion

Hypercholesterolemia may alter MMP1 and ADAMTS5 expression in the synovium of the glenohumeral joint.

Background

Several systemic factors have been linked with degenerative shoulder diseases, including dyslipidemia, diabetes and obesity [1,2,3]. Hypercholesterolemia is a systemic metabolic disease characterized by abnormally high levels of cholesterol in the blood which has effects on not only internal organs and cardiovascular tissues but also the musculoskeletal system [4]. Previous studies have focused on the effect of hypercholesterolemia on the rotator cuff [5,6,7]. However, an evaluation of comorbidities in patients presenting with shoulder osteoarthritis (OA) revealed that 48.7% of patients with primary shoulder OA also suffered from hyperlipidemia [8]. Hypercholesterolemia has also been statistically associated with glenohumeral joint pain but not rotator cuff tendinopathy [9]. Notably, hypercholesterolemia has also been linked with OA in the knee and hand [10, 11]. These observations suggest that hypercholesterolemia affects not only tendons but also joint pathology in the shoulder. Nevertheless, the effect of hyperlipidemia on the glenohumeral joint remains unclear.

The matrix metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase Domain with Thrombospondin motifs (ADAMTS) family play a critical role in the destruction of extracellular matrix in arthritis, rotator cuff disease and other musculoskeletal diseases [12,13,14,15]. Synovial tissue is a major source of MMPs and ADAMTS, the expression of which could be affected by dyslipidemia [16, 17]. We previously found that dyslipidemia altered synovial MMP and ADAMTS expression levels in a mouse model of knee OA that exhibited dyslipidemia [16]. Previous studies reported the elevation of MMPs in tendons in patients with tendinopathy [14] and that this elevation was affected by hypercholesterolemia [4]. However, it remains unclear whether dyslipidemia alters MMPs and ADAMTS expression in the synovium of the glenohumeral joint.

Here, we evaluated the mRNA expression of MMP and ADAMTS in the glenohumeral synovium of patients with and without dyslipidemia.

Methods

Patients

This study was approved by the Ethics Committee of our institution (Clinical Research Review Board of the Kitasato Institute; reference number KMEO B13-113) and abode by the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all participants.

Synovial membrane samples acquired from the glenohumeral joint, specifically areas of the rotator interval showing redness, were obtained from patients who underwent arthroscopic surgery from November 2017 to October 2020. Patients with RCT were clinically assessed prior to surgery using the Constant score [18]. We graded radiographic OA as normal (no osteophytes), mild (< 3 mm), moderate (3–7 mm), or severe (≥ 7 mm) using the Samilson–Prieto classification [19]. All arthroscopic surgeries to repair a torn rotator cuff were performed by an experienced shoulder surgeon. We excluded patients with a history of rheumatoid arthritis, other collagen diseases, and fractures in the humerus or glenoid. The remaining patients were divided into two groups according to their total cholesterol (TC) level (< 220 mg/dl and ≥ 220 mg/dl), based on the standardized value established by the Japan Atherosclerosis Society (JAS) [20]. Patients were also divided into two groups according to triglyceride (TG) levels (< 150 mg/dl and ≥ 150 mg/dl), also based on the standardized value of the JAS [20].

qPCR

To extract total RNA, synovial samples were homogenized using a Polytron homogenizer (KINEMATICA AG, Luzerne Strasse, Luzern, Switzerland). After centrifugation (18,000×g, 4 °C, 5 min), the supernatants were mixed with an equal volume of 100% ethanol solution, vortexed for 30 s, and then immediately transferred to spin columns (Direct-zol RNA MicroPrep kit; Zymo Research, Irvine, CA, USA) for mRNA isolation. RNA concentration was determined using a DS-11 spectrophotometer (DeNovix, Wilmington, DE, USA). SuperScript™ III Reverse Transcriptase (Thermo Fisher Scientific, Waltham, MA, USA) was used for complementary DNA synthesis. We quantitatively measured the gene expression of ADAMTSs (ADAMTS4 and ADAMTS5) and MMPs (MMP1, 3, 9, and 13) on a real-time PCR detection system (CFX-96; Bio-Rad, Hercules, CA, USA). The PCR primer pair sequences are listed in Table 1. mRNA expression of the ADAMTS and MMP genes was normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) using the delta-delta Ct method. When the average expression (genes/GAPDH) level in the low HC group was 1, the relative expression was calculated.

Table 1 Sequences of primers

Statistical analysis

Results are expressed as mean ± standard deviation (SD). Statistical significance was determined using the nonparametric Mann–Whitney U test or unpaired t-test. Statistical significance was set at P < 0.05. All statistical analyses were conducted using the SSPS software v19.0 (IBM, USA).

Results

Expression of ADAMTS and MMPS in patients with low and high TC levels

The clinical characteristics of patients are summarized in Table 2. Briefly, 42 patients were assigned to the low TC group (27 men and 15 women, aged 65 ± 9 years) and 31 patients were assigned to the high TC group (23 men and 8 women, aged 64 ± 11 years; Table 2). In both groups, no significant differences were observed in patient age at surgery (P = 0.505), men/women ratio (P = 0.449), body mass index (P = 0.539), TG levels (P = 0.018), Constant score (P = 0.668), or tear size (P = 0.465). ADAMTS5 and MMP1 levels were significantly higher in the high-TC group than in the low-TC group (ADAMTS5, P = 0.023; MMP1, P = 0.025; Fig. 1b, c). In contrast, no significant differences were observed for ADAMTS4 and MMP3, 9, and 13 (ADAMTS4, P = 0.547; MMP3, P = 0.55; MMP9, P = 0.521; MMP13, P = 0.785; Fig. 1a, d, e, f).

Table 2 Clinical characteristics of low and high total cholesterol (TC) groups
Fig. 1
figure 1

Effect of cholesterol levels on the mRNA expression of MMPs and ADAMTSs mRNA expression levels of a MMP1, b MMP3, c MMP9, d MMP13, e ADAMTS4, f ADAMTS5

Expression of ADAMTS and MMPs in patients with low and high TG levels

According to the criteria, 33 patients were assigned to the low-TG group (16 men and 17 women, aged 65 ± 8 years) and 40 patients were assigned to the high-TG group (34 men and 6 women, aged 64 ± 11 years; Table 3). No significant differences between groups were found in the average age of patients at surgery (P = 0.846), body mass index (P = 0.094), total cholesterol level (P = 0.202), Constant score (P = 0.549), or tear size (P = 0.516). However, significant differences were observed in the men/women ratio (P = 0.001). No significant differences in mRNA expression levels were detected between the two groups (Fig. 2).

Table 3 Clinical characteristics of low and high total triglyceride (TG) groups
Fig. 2
figure 2

Effect of triglyceride levels on the mRNA expression of MMPs and ADAMTSs a mRNA expression levels of MMP1, b MMP3, c MMP9, d MMP13, e ADAMTS4, and f ADAMTS5

Discussion

In this study, ADAMTS5 and MMP1 expression in the synovial membrane of the glenohumeral joint was found to be significantly higher in patients with high TC levels than in those with low TC levels. In contrast, no significant differences were observed between the two TG groups. Therefore, hypercholesterolemia altered synovial MMP1 and ADAMTS5 levels in the glenohumeral joint.

MMP-1 is primarily produced by the synovial cells that line the joints [12]. MMP-1 has the unique ability to cleave the triple helix of collagen. Cleavage allows the chains to unwind, which makes them susceptible to further degradation by other MMPs [21]. A relationship between MMP1 expression and cholesterol levels has been identified in both in vitro and in vivo animal studies [22,23,24]. Cholesterol crystals stimulate MMP1 mRNA expression in human macrophages in vitro [22]. Oxidized LDL promotes MMP1 production in cultured synoviocytes derived from patients with rheumatoid arthritis [23]. Hypercholesterolemic rabbits exhibited increased MMP1 levels in the aorta [24]. In this study, MMP1 expression in the glenohumeral synovia was confirmed to significantly differ between patients with high and low TC levels, although this was not confirmed between patients with high and low TG levels. Rotator cuff MMP1 levels in synovial fluid are higher in patients with rotator tears than in healthy controls [25]. MMP1 levels in RCT patients with a massive full thickness tear were significantly higher than in patients with a partial-thickness tear and a non-massive full-thickness tear [26]. In our study, tear size did not differ tear between the high TC and low TC groups, suggesting the possibility that hypercholesterolemia increases MMP1 levels in the glenohumeral joint.

ADAMTS5 has emerged as a principal mediator of aggrecan loss in OA [27, 28]. ADAMTS-5 knockout mice were reportedly protected from synovitis and joint destruction [29, 30]. Some studies have focused on the relationship between ADAMTS5 and cholesterol levels. ADAMTS5 was elevated in the nucleus pulposus cells of APO-E knockout rabbits [31]. Intra-articular anti-ADAMTS5 antibody slowed down the progression of OA in a dose-dependent manner in a murine OA model with hypercholesterolemia [32]. We found that patients with hypercholesterolemia had higher expression levels of synovial ADAMTS5. A previous study reported that cartilage obtained from patients with shoulder OA had higher ADAMTS5 mRNA expression than cartilage obtained from non-OA patients [33]. Some of our present patients had OA. However, no significant difference was found in OA grade in the high and low TC groups. Therefore, our findings suggest that hypercholesterolemia might also affect ADAMTS5 expression in the glenohumeral synovium.

Several studies have reported a possible association between knee OA and TG levels, albeit that none of these associations reached statistical significance [10, 34, 35]. In our study, expression of MMPs and ADAMTSs did not differ between patients with low and high TG levels. Corroborating previous findings [10, 34, 35], our study suggests that the presence of hypertriglyceridemia has less influence on the glenohumeral joint.

Hypercholesterolemia leads to structural, inflammatory and mechanical changes in tendons, which predispose hypercholesterolemic patients to a greater risk of tendon pathology [4]. Shoulder arthritis can occur in patients with RCT, and in severe cases, the cartilage degeneration may be related to extra mechanical loading resulting from the rotator insufficiency [36]. Given that impaired mechanical loading increases MMP1 and ADAMTS5 in synovial cells [37, 38], our results might partly reflect the upregulation of mechanical stress factors due to tendinopathy. Further investigation using non-RCT patients may help reveal the direct link between synovial pathology and hypercholesterolemia.

Several limitations of this study warrant mention. First, the major limitation is that the only measure used was PCR. Protein profiling studies such as western blot and immunohistochemical analysis are needed to validate our gene expression profile results. Second, we did not include a healthy control population, although this would have been preferable as an ideal control group. Finally, any directly link in the etiology of OA with MMP1 and ADAMTS5 remains unclear.

Conclusions

Hypercholesterolemia may alter MMP1 and ADAMTS5 expression in synovium of the glenohumeral joint.

Availability of data and materials

Datasets supporting the conclusions of this article are included within the article. The raw data can be requested from the corresponding author.

Abbreviations

OA:

Osteoarthritis

ADAMTSs:

A Disintegrin and Metalloprotease with Thrombospondin Motifs

MMPs:

Matrix metalloproteases

RCTs:

Rotator cuff tears

TC:

Total cholesterol

TG:

Triglyceride

JAS:

Japan Atherosclerosis Society

SD:

Standard deviation

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  1. Juel NG, Brox JI, Hellund JC, Holte KB, Berg TJ. The prevalence of radiological glenohumeral osteoarthritis in long-term type 1 diabetes: the Dialong shoulder study. Scand J Rheumatol. 2018;47(4):325–30.

    Article  CAS  Google Scholar 

  2. Juel NG, Brox JI, Hellund JC, Merckoll E, Holte KB, Berg TJ. Radiological glenohumeral osteoarthritis in long-term type 1 diabetes. Prevalence and reliability of three classification systems. The Dialong shoulder study. Skeletal Radiol 2018, 47(9):1245–51.

  3. Wall KC, Politzer CS, Chahla J, Garrigues GE. Obesity is associated with an increased prevalence of glenohumeral osteoarthritis and arthroplasty: a cohort study. Orthop Clin North Am. 2020;51(2):259–64.

    Article  Google Scholar 

  4. Yang Y, Lu H, Qu J. Tendon pathology in hypercholesterolaemia patients: epidemiology, pathogenesis and management. J Orthop Translat. 2019;16:14–22.

    Article  Google Scholar 

  5. Abboud JA, Kim JS. The effect of hypercholesterolemia on rotator cuff disease. Clin Orthop Relat Res. 2010;468(6):1493–7.

    Article  Google Scholar 

  6. Djerbi I, Chammas M, Mirous MP, Lazerges C, Coulet B. Impact of cardiovascular risk factor on the prevalence and severity of symptomatic full-thickness rotator cuff tears. Orthop Traumatol Surg Res. 2015;101(6 Suppl):S269-273.

    Article  CAS  Google Scholar 

  7. Oliva F, Osti L, Padulo J, Maffulli N. Epidemiology of the rotator cuff tears: a new incidence related to thyroid disease. Muscles Ligaments Tendons J. 2014;4(3):309–14.

    Article  Google Scholar 

  8. Schoenfeldt TL, Trenhaile S, Olson R. Glenohumeral osteoarthritis: frequency of underlying diagnoses and the role of arm dominance-a retrospective analysis in a community-based musculoskeletal practice. Rheumatol Int. 2018;38(6):1023–9.

    Article  Google Scholar 

  9. Applegate KA, Thiese MS, Merryweather AS, Kapellusch J, Drury DL, Wood E, Kendall R, Foster J, Garg A, Hegmann KT. Association between cardiovascular disease risk factors and rotator cuff tendinopathy: a cross-sectional study. J Occup Environ Med. 2017;59(2):154–60.

    Article  Google Scholar 

  10. Hart DJ, Doyle DV, Spector TD. Association between metabolic factors and knee osteoarthritis in women: the Chingford Study. J Rheumatol. 1995;22(6):1118–23.

    CAS  PubMed  Google Scholar 

  11. Sturmer T, Sun Y, Sauerland S, Zeissig I, Gunther KP, Puhl W, Brenner H: Serum cholesterol and osteoarthritis. The baseline examination of the Ulm Osteoarthritis Study. J Rheumatol 1998, 25(9):1827–32.

  12. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006;11:529–43.

    Article  CAS  Google Scholar 

  13. Davidson RK, Waters JG, Kevorkian L, Darrah C, Cooper A, Donell ST, Clark IM. Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage. Arthritis Res Ther. 2006;8(4):R124.

    Article  Google Scholar 

  14. Del Buono A, Oliva F, Osti L, Maffulli N. Metalloproteases and tendinopathy. Muscles Ligaments Tendons J. 2013;3(1):51–7.

    Article  Google Scholar 

  15. Wang WJ, Yu XH, Wang C, Yang W, He WS, Zhang SJ, Yan YG, Zhang J. MMPs and ADAMTSs in intervertebral disc degeneration. Clin Chim Acta. 2015;448:238–46.

    Article  CAS  Google Scholar 

  16. Uchida K, Satoh M, Inoue G, Onuma K, Miyagi M, Iwabuchi K, Takaso M. CD11c(+) macrophages and levels of TNF-alpha and MMP-3 are increased in synovial and adipose tissues of osteoarthritic mice with hyperlipidaemia. Clin Exp Immunol. 2015;180(3):551–9.

    Article  CAS  Google Scholar 

  17. Villalvilla A, Larranaga-Vera A, Lamuedra A, Perez-Baos S, Lopez-Reyes AG, Herrero-Beaumont G, Largo R. Modulation of the inflammatory process by hypercholesterolemia in osteoarthritis. Front Med (Lausanne) 2020, 7:566250.

  18. Constant CR, Murley AH. A clinical method of functional assessment of the shoulder. Clin Orthop Relat Res. 1987;214:160–4.

    Article  Google Scholar 

  19. Brox JI, Lereim P, Merckoll E, Finnanger AM. Radiographic classification of glenohumeral arthrosis. Acta Orthop Scand. 2003;74(2):186–9.

    Article  Google Scholar 

  20. Hata Y, Mabuchi H, Saito Y, Itakura H, Egusa G, Ito H, Teramoto T, Tsushima M, Tada N, Oikawa S, et al. Report of the Japan Atherosclerosis Society (JAS) guideline for diagnosis and treatment of hyperlipidemia in Japanese adults. J Atheroscler Thromb. 2002;9(1):1–27.

    Article  Google Scholar 

  21. Vincenti MP, Brinckerhoff CE. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res. 2002;4(3):157–64.

    Article  CAS  Google Scholar 

  22. Corr EM, Cunningham CC, Dunne A. Cholesterol crystals activate Syk and PI3 kinase in human macrophages and dendritic cells. Atherosclerosis. 2016;251:197–205.

    Article  CAS  Google Scholar 

  23. Ishikawa M, Ito H, Akiyoshi M, Kume N, Yoshitomi H, Mitsuoka H, Tanida S, Murata K, Shibuya H, Kasahara T, et al. Lectin-like oxidized low-density lipoprotein receptor 1 signal is a potent biomarker and therapeutic target for human rheumatoid arthritis. Arthritis Rheum. 2012;64(4):1024–34.

    Article  CAS  Google Scholar 

  24. Um MY, Hwang KH, Choi WH, Ahn J, Jung CH, Ha TY. Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits. Nutr Res. 2014;34(10):886–93.

    Article  CAS  Google Scholar 

  25. Shih CA, Wu KC, Shao CJ, Chern TC, Su WR, Wu PT, Jou IM. Synovial fluid biomarkers: association with chronic rotator cuff tear severity and pain. J Shoulder Elbow Surg. 2018;27(3):545–52.

    Article  Google Scholar 

  26. Yoshihara Y, Hamada K, Nakajima T, Fujikawa K, Fukuda H. Biochemical markers in the synovial fluid of glenohumeral joints from patients with rotator cuff tear. J Orthop Res. 2001;19(4):573–9.

    Article  CAS  Google Scholar 

  27. Apte SS. Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis. Biochem J. 2016;473(1):e1-4.

    Article  CAS  Google Scholar 

  28. Little CB, Meeker CT, Golub SB, Lawlor KE, Farmer PJ, Smith SM, Fosang AJ. Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair. J Clin Invest. 2007;117(6):1627–36.

    Article  CAS  Google Scholar 

  29. Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature. 2005;434(7033):644–8.

    Article  CAS  Google Scholar 

  30. Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature. 2005;434(7033):648–52.

    Article  CAS  Google Scholar 

  31. Beierfuss A, Hunjadi M, Ritsch A, Kremser C, Thome C, Mern DS. APOE-knockout in rabbits causes loss of cells in nucleus pulposus and enhances the levels of inflammatory catabolic cytokines damaging the intervertebral disc matrix. PLoS One 2019, 14(11):e0225527.

  32. Brewster M, Lewis EJ, Wilson KL, Greenham AK, Bottomley KM. Ro 32–3555, an orally active collagenase selective inhibitor, prevents structural damage in the STR/ORT mouse model of osteoarthritis. Arthritis Rheum. 1998;41(9):1639–44.

    Article  CAS  Google Scholar 

  33. Casagrande D, Stains JP, Murthi AM. Identification of shoulder osteoarthritis biomarkers: comparison between shoulders with and without osteoarthritis. J Shoulder Elbow Surg. 2015;24(3):382–90.

    Article  Google Scholar 

  34. Al-Arfaj AS. Radiographic osteoarthritis and serum cholesterol. Saudi Med J. 2003;24(7):745–7.

    PubMed  Google Scholar 

  35. Davies-Tuck ML, Hanna F, Davis SR, Bell RJ, Davison SL, Wluka AE, Adams J, Cicuttini FM. Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women: a prospective cohort study. Arthritis Res Ther. 2009;11(6):R181.

    Article  Google Scholar 

  36. Eajazi A, Kussman S, LeBedis C, Guermazi A, Kompel A, Jawa A, Murakami AM. Rotator cuff tear arthropathy: pathophysiology, imaging characteristics, and treatment options. AJR Am J Roentgenol. 2015;205(5):W502-511.

    Article  Google Scholar 

  37. Jamal J, Roebuck MM, Lee SY, Frostick SP, Abbas AA, Merican AM, Teo SH, Wood A, Tan SL, Bou-Gharios G et al. Modulation of the mechanical responses of synovial fibroblasts by osteoarthritis-associated inflammatory stressors. Int J Biochem Cell Biol 2020, 126:105800.

  38. Sun I, Liu Y, Tanaka SM, Lee CW, Sun HB, Yokota H. Effects of high-impact mechanical loading on synovial cell cultures. J Sports Sci Med. 2004;3(1):37–43.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to Yuko Onuki for her helpful support during the study.

Funding

This investigation was supported in part by Grant-in-Aid for Early-Career Scientists Grant No. 21K16716.

Author information

Authors and Affiliations

Authors

Contributions

KM, TK, KU, MN, RT, DI, and MS acquired the data. GI and MT analyzed and interpreted the data. All authors are responsible for the study concept and design, and contributed to writing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kyoko Muneshige.

Ethics declarations

Ethics approval and consent to participate

This study was conducted with the approval of the Ethics Committee at our institution (Clinical Research Review Board of the Kitasato Institute; reference number KMEO B13-113) and abides by the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Muneshige, K., Uchida, K., Kenmoku, T. et al. Elevation of MMP1 and ADAMTS5 mRNA expression in glenohumeral synovia of patients with hypercholesterolemia. J Orthop Surg Res 17, 97 (2022). https://doi.org/10.1186/s13018-022-02998-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13018-022-02998-6

Keywords

  • Osteoarthritis
  • Hypercholesterolemia
  • ADAMTS5
  • MMP1
  • Synovium