The collagenases: are they tractable targets for preventing cartilage destruction in osteoarthritis?

References

• Huang Z, Ding C, Li T, et al. Current status and future prospects for disease modification in osteoarthritis. Rheumatology (Oxford). [2018 May 1];57(suppl_4):iv108–iv123.
   PubMedGoogle Scholar
• Creamer P, Hochberg MC. Osteoarthritis. Lancet. [1997 Aug 16];350(9076):503–508.
   PubMed Web of Science ®Google Scholar
• Barter M, Bui C, Young D. Epigenetic mechanisms in cartilage and osteoarthritis: DNA methylation, histone modifications and microRNAs. Osteoarthritis Cartilage. 2012;20(5):339–349.
   PubMed Web of Science ®Google Scholar
• Loughlin J. The genetic epidemiology of human primary osteoarthritis: current status. Expert Rev Mol Med. [2005 May 24];7(9):1–12.
   PubMedGoogle Scholar
• Tanna S. Osteoarthritis “Opportunities to address pharmaceutical gaps.” Priority Med Europe World. 2004;6(12):3–23.
   Google Scholar
• Wang M, Sampson ER, Jin H, et al. MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis Res Ther. [2013 Jan 8];15(1):R5.
   PubMed Web of Science ®Google Scholar
• Jeon OH, David N, Campisi J, et al. Senescent cells and osteoarthritis: a painful connection. J Clin Invest. [2018 Apr 2];128(4):1229–1237.
   PubMed Web of Science ®Google Scholar
• Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001 Jun;44(6):1237–1247.
   PubMed Web of Science ®Google Scholar
• Mehana E-SE, Khafaga AF, El-Blehi SS. The role of matrix metalloproteinases in osteoarthritis pathogenesis: an updated review. Life Sci. 2019;234:116786.
   PubMed Web of Science ®Google Scholar
• Peterson JT. The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors. Cardiovasc Res. [2006 Feb 15];69(3):677–687.
   PubMed Web of Science ®Google Scholar
• Felson DT, Neogi T. Emerging treatment models in rheumatology: challenges for osteoarthritis trials. Arthritis Rheumatol. 2018 Aug;70(8):1175–1181.
   PubMedGoogle Scholar
• Okada Y. Matrix-degrading metalloproteinases and their roles in joint destruction. Mod Rheumatol. 2000 Sep;10(3):121–128.
   PubMedGoogle Scholar
• Bora JF, Miller G. Joint physiology, cartilage metabolism, and the etiology of osteoarthritis. Hand Clin. 1987;3(3):325.
   PubMed Web of Science ®Google Scholar
• Jahn S, Klein J. Lubrication of articular cartilage. Phys Today. 2018;71(4):48–54.
   Web of Science ®Google Scholar
• Johnson ZI, Shapiro IM, Risbud MV. Extracellular osmolarity regulates matrix homeostasis in the intervertebral disc and articular cartilage: evolving role of tonebp. Matrix Biol. 2014;40:10–16.
   PubMed Web of Science ®Google Scholar
• Guilak F, Nims RJ, Dicks A, et al. Osteoarthritis as a disease of the cartilage pericellular matrix. Matrix Biol. 2018;71:40–50.
   PubMed Web of Science ®Google Scholar
• Li H, Wang D, Yuan Y, et al. New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Res Ther. [2017 Nov 10];19(1):248.
   PubMedGoogle Scholar
• Poole AR. Cartilage in health and disease; arthritis and allied conditions: a textbook of rheumatology. 14th. Koopman W, editor. Philadelphia: Lippincott Williams & Wilkins; 2001.
   Google Scholar
• Malfait A, Tortorella M. The “elusive DMOAD”: aggrecanase inhibition from laboratory to clinical. Clin Exp Rheumatol. 2019;37(Suppl 120):S130–34.
   PubMedGoogle Scholar
• Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006;11(1):529–543.
   PubMedGoogle Scholar
• Bruckner P, van der Rest M. Structure and function of cartilage collagens. Microsc Res Tech. [1994 Aug 1];28(5):378–384.
   PubMed Web of Science ®Google Scholar
• Anderson DD, Chubinskaya S, Guilak F, et al. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res. Jun 2011;29(6):802–809.
   PubMed Web of Science ®Google Scholar
• Saberi Hosnijeh F, Bierma-Zeinstra SM, Bay-Jensen AC. Osteoarthritis year in review 2018: biomarkers (biochemical markers). Osteoarthritis Cartilage. 2019 Mar;27(3):412–423.
   PubMed Web of Science ®Google Scholar
• Robinson WH, Lepus CM, Wang Q, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. Oct 2016;12(10):580–592.
   PubMed Web of Science ®Google Scholar
• Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011 Sep;23(5):471–478.
   PubMed Web of Science ®Google Scholar
• Malfait AM, Miller RJ. Emerging targets for the management of osteoarthritis pain. Curr Osteoporos Rep. 2016 Dec;14(6):260–268.
   PubMed Web of Science ®Google Scholar
• Nam J, Aguda BD, Rath B, et al. Biomechanical thresholds regulate inflammation through the NF-kappaB pathway: experiments and modeling. PLoS One. 2009;4(4):e5262.
   PubMed Web of Science ®Google Scholar
• Fransen M, McConnell S, Bell M. Therapeutic exercise for people with osteoarthritis of the hip or knee. A systematic review. J Rheumatol. 2002 Aug;29(8):1737–1745.
   PubMed Web of Science ®Google Scholar
• Honorati MC, Bovara M, Cattini L, et al. Contribution of interleukin 17 to human cartilage degradation and synovial inflammation in osteoarthritis. Osteoarthritis Cartilage. Oct 2002;10(10):799–807.
   PubMed Web of Science ®Google Scholar
• Vincent TL, Watt FE. Osteoarthritis. Medicine (Baltimore). [2014 apr 01]2014;42(4):213–219.
   Google Scholar
• Carr AJ. Beyond disability: measuring the social and personal consequences of osteoarthritis. Osteoarthritis Cartilage. 1999 Mar;7(2):230–238.
   PubMed Web of Science ®Google Scholar
• Creamer P. Osteoarthritis pain and its treatment. Curr Opin Rheumatol. 2000 Sep;12(5):450–455.
   PubMed Web of Science ®Google Scholar
• Creamer P, Lethbridge-Cejku M, Hochberg MC. Factors associated with functional impairment in symptomatic knee osteoarthritis. Rheumatology (Oxford). 2000 May;39(5):490–496.
   PubMed Web of Science ®Google Scholar
• Wieland HA, Michaelis M, Kirschbaum BJ, et al. Osteoarthritis—an untreatable disease? Nat Rev Drug Discov. 2005;4(4):331.
   PubMed Web of Science ®Google Scholar
• Pauli C, Whiteside R, Heras FL, et al. Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development. Osteoarthritis Cartilage. Jun 2012;20(6):476–485.
   PubMed Web of Science ®Google Scholar
• Jung YK, Han MS, Park HR, et al. Calcium-phosphate complex increased during subchondral bone remodeling affects early stage osteoarthritis. Sci Rep. [2018 Jan 11];8(1):487.
   PubMedGoogle Scholar
• Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther. 2003;5(2):94.
   PubMed Web of Science ®Google Scholar
• Malemud CJ. Pharmacologic interventions for preventing chondrocyte apoptosis in rheumatoid arthritis and osteoarthritis. Drug Discovery. 2018;45:77.
   Google Scholar
• Karsdal MA, Madsen SH, Christiansen C, et al. Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity. Arthritis Res Ther. 2008;10(3):R63.
   PubMed Web of Science ®Google Scholar
• Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta. 2012 Jan;1824(1):133–145.
   PubMed Web of Science ®Google Scholar
• Goldring SR, Goldring MB. Clinical aspects, pathology and pathophysiology of osteoarthritis. J Musculoskelet Neuronal Interact. 2006 Oct-Dec;6(4):376–378.
   PubMedGoogle Scholar
• Orlowsky EW, Kraus VB. The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol. 2015 Mar;42(3):363–371.
   PubMed Web of Science ®Google Scholar
• Sorsa T, Tjaderhane L, Konttinen YT, et al. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med. 2006;38(5):306–321.
   PubMed Web of Science ®Google Scholar
• Kuula H, Salo T, Pirila E, et al. Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis. Infect Immun. Feb 2009;77(2):850–859.
   PubMed Web of Science ®Google Scholar
• van Den Berg WB. Osteoarthritis year 2010 in review: pathomechanisms. Osteoarthritis Cartilage. 2011 Apr;19(4):338–341.
   PubMed Web of Science ®Google Scholar
• Tchetverikov I, Lohmander LS, Verzijl N, et al. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis. May 2005;64(5):694–698.
   PubMed Web of Science ®Google Scholar
• Gross J, Lapiere CM. Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci U S A. [1962 Jun 15]; 48(6):1014–1022.
   PubMed Web of Science ®Google Scholar
• Woessner JF Jr. Catabolism of collagen and non-collagen protein in the rat uterus during post-partum involution. Biochem J. 1962 May;83(2):304–314.
   PubMed Web of Science ®Google Scholar
• Yoshihara Y, Nakamura H, Obata K, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis. Jun 2000;59(6):455–461.
   PubMed Web of Science ®Google Scholar
• Djuric T, Zivkovic M. Overview of MMP biology and gene associations in human diseases. Role Matrix Met Hum Body Pathol. 2017;1:3–33.
   Google Scholar
• Mirastschijski U, Schnabel R, Claes J, et al. Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function. Wound Repair Regen. Mar-Apr 2010;18(2):223–234.
   PubMed Web of Science ®Google Scholar
• Golub LM, Sorsa T, Lee HM, et al. Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J Clin Periodontol. Feb 1995;22(2):100–109.
   PubMed Web of Science ®Google Scholar
• Teronen O, Laitinen M, Salo T, et al. Inhibition of matrix metalloproteinases by bisphosphonates may in part explain their effects in the treatment of multiple myeloma. Blood. [2000 Dec 1];96(12):4006–4007.
   PubMed Web of Science ®Google Scholar
• Gendron R, Grenier D, Sorsa T, et al. Inhibition of the activities of matrix metalloproteinases 2, 8, and 9 by chlorhexidine. Clin Diagn Lab Immunol. May 1999;6(3):437–439.
   PubMedGoogle Scholar
• Hayami T, Zhuo Y, Wesolowski GA, et al. Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis. Bone. Jun 2012;50(6):1250–1259.
   PubMed Web of Science ®Google Scholar
• McDougall JJ, Schuelert N, Bowyer J. Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea pig model of spontaneous osteoarthritis. Osteoarthritis Cartilage. 2010 Oct;18(10):1355–1357.
   PubMed Web of Science ®Google Scholar
• Verma RP, Hansch C. Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs. Bioorg Med Chem. [2007 Mar 15];15(6):2223–2268.
   PubMed Web of Science ®Google Scholar
• Laronha H, Caldeira J. Structure and function of human matrix metalloproteinases. Cells. [2020 Apr 26];9(5):1076.
   Web of Science ®Google Scholar
• Khuda F, Najmi Mohamad Anuar N, Baharin B, et al. A mini review on the associations of matrix metalloproteinases (MMPs) −1, −8, −13 with periodontal disease. AIMS Mol Sci. 2021;8(1):13–31.
   Web of Science ®Google Scholar
• Alipour H, Raz A, Zakeri S, et al. Therapeutic applications of collagenase (metalloproteases): a review. Asia Pac J Biomed. 2016;6(11):975–981.
   Web of Science ®Google Scholar
• Paiva KB, Granjeiro JM. Bone tissue remodeling and development: focus on matrix metalloproteinase functions. Arch Biochem Biophys. [2014 Nov 1];561:74–87.
   PubMed Web of Science ®Google Scholar
• Lauhio A, Farkkila E, Pietilainen KH, et al. Association of MMP-8 with obesity, smoking and insulin resistance. Eur J Clin Invest. Sep 2016;46(9):757–765.
   PubMed Web of Science ®Google Scholar
• Yoshihara Y, Nakamura H, Obata K, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis. 2000;59(6):455–461.
   PubMed Web of Science ®Google Scholar
• Mohan V, Talmi-Frank D, Arkadash V, et al. Matrix metalloproteinase protein inhibitors: highlighting a new beginning for metalloproteinases in medicine. Metalloproteinases Med. 2016;3:31.
   Google Scholar
• Iyer RP, Patterson NL, Fields GB, et al. The history of matrix metalloproteinases: milestones, myths, and misperceptions. Am J Physiol Heart Circ Physiol. 2012;303(8):H919–H930.
   PubMed Web of Science ®Google Scholar
• Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2(3):161–174.
   PubMed Web of Science ®Google Scholar
• Murphy G, Nagase H. Progress in matrix metalloproteinase research. Mol Aspects Med. 2008;29(5):290–308.
   PubMed Web of Science ®Google Scholar
• Vilen S-T, Salo T, Sorsa T, et al. Fluctuating roles of matrix metalloproteinase-9 in oral squamous cell carcinoma. Sci World J. 2013;2013:1–11.
   Google Scholar
• Johnson LL, Dyer R, Hupe DJ. Matrix metalloproteinases. Curr Opin Chem Biol. 1998 Aug;2(4):466–471.
   PubMed Web of Science ®Google Scholar
• Kumar D, Gupta SP. A quantitative structure-activity relationship study on some matrix metalloproteinase and collagenase inhibitors. Bioorg Med Chem. [2003 Feb 6];11(3):421–426.
   PubMed Web of Science ®Google Scholar
• Harper E, Bloch KJ, Gross J. The zymogen of tadpole collagenase. Biochemistry. [1971 Aug 3];10(16):3035–3041.
   PubMed Web of Science ®Google Scholar
• Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem. 1999;274(31):21491–21494.
   PubMed Web of Science ®Google Scholar
• Shlopov BV, Lie WR, Mainardi CL, et al. Osteoarthritic lesions. Involvement of three different collagenases. Arthritis Rheum. 1997;40(11):2065–2074.
   PubMedGoogle Scholar
• Reboul P, Pelletier J-P, Tardif G, et al. The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. A role in osteoarthritis. J Clin Invest. 1996;97(9):2011–2019.
   PubMed Web of Science ®Google Scholar
• Mitchell PG, Magna HA, Reeves LM, et al. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest. [1996 Feb 1];97(3):761–768.
   PubMed Web of Science ®Google Scholar
• Freije JM, Diez-Itza I, Balbin M, et al. Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem. [1994 Jun 17];269(24):16766–16773.
   PubMed Web of Science ®Google Scholar
• 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):157–164.
   PubMedGoogle Scholar
• Shiomi T, Lemaitre V, D’Armiento J, et al. Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol Int. 2010 Jul;60(7):477–496.
   PubMed Web of Science ®Google Scholar
• Roach HI, Yamada N, Cheung KS, et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum. Oct 2005;52(10):3110–3124.
   PubMed Web of Science ®Google Scholar
• Park SJ, Cheon EJ, Lee MH, et al. MicroRNA‐127‐5p regulates matrix metalloproteinase 13 expression and interleukin‐1β–induced catabolic effects in human chondrocytes. Arthritis Rheumatism. 2013;65(12):3141–3152.
   PubMedGoogle Scholar
• Ge X, Ma X, Meng J, et al. Role of wnt‐5A in interleukin‐1β–induced matrix metalloproteinase expression in rabbit temporomandibular joint condylar chondrocytes. Arthritis Rheumatism. 2009;60(9):2714–2722.
   PubMedGoogle Scholar
• Fosang AJ, Last K, Knäuper V, et al. Degradation of cartilage aggrecan by collagenase‐3 (MMP‐13). FEBS Lett. 1996;380(1–2):17–20.
   PubMed Web of Science ®Google Scholar
• Chakraborti S, Mandal M, Das S, et al. Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem. Nov 2003;253(1–2):269–285.
   PubMed Web of Science ®Google Scholar
• Fosang AJ, Last K, Neame PJ, et al. Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan. Biochem J. [1994 Dec 1];304(Pt 2):347–351.
   PubMedGoogle Scholar
• Yamamoto K, Santamaria S, Botkjaer KA, et al. Inhibition of shedding of low-density lipoprotein receptor-related protein 1 reverses cartilage matrix degradation in osteoarthritis. Arthritis Rheumatol. Jun 2017;69(6):1246–1256.
   PubMed Web of Science ®Google Scholar
• Salminen-Mankonen HJ, Morko J, Vuorio E. Role of cathepsin K in normal joints and in the development of arthritis. Curr Drug Targets. 2007 Feb;8(2):315–323.
   PubMed Web of Science ®Google Scholar
• Wang D, Li W, Pechar M, et al. Cathepsin K inhibitor–polymer conjugates: potential drugs for the treatment of osteoporosis and rheumatoid arthritis. Int J Pharm. 2004;277(1–2):73–79.
   PubMedGoogle Scholar
• Everts V, Delaisse JM, Korper W, et al. Degradation of collagen in the bone-resorbing compartment underlying the osteoclast involves both cysteine-proteinases and matrix metalloproteinases. J Cell Physiol. 1992 Feb;150(2):221–231.
   PubMed Web of Science ®Google Scholar
• Woolley DE, Roberts DR, Evanson JM. Small molecular weight beta 1 serum protein which specifically inhibits human collagenases. Nature. [1976 May 27];261(5558):325–327.
   PubMed Web of Science ®Google Scholar
• Oh J, Takahashi R, Kondo S, et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell. [2001 Dec 14];107(6):789–800.
   PubMed Web of Science ®Google Scholar
• Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta. [2000 Mar 7];1477(1–2):267–283.
   PubMedGoogle Scholar
• Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci. [2002 Oct 1];115(Pt 19):3719–3727.
   PubMed Web of Science ®Google Scholar
• Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst. [2001 Feb 7];93(3):178–193.
   PubMedGoogle Scholar
• Hoekstra R, Eskens FA, Verweij J. Matrix metalloproteinase inhibitors: current developments and future perspectives. Oncologist. 2001;6(5):415–427.
   PubMed Web of Science ®Google Scholar
• Bauer EA, Eisen AZ, Jeffrey JJ. Regulation of vertebrate collagenase activity in vivo and in vitro. J Invest Dermatol. 1972 Jul;59(1):50–55.
   PubMed Web of Science ®Google Scholar
• Close DR. Matrix metalloproteinase inhibitors in rheumatic diseases. Ann Rheum Dis. 2001 Nov;60(Suppl 3):iii62–7.
   PubMed Web of Science ®Google Scholar
• Neuman P, Dahlberg LE, Englund M, et al. Concentrations of synovial fluid biomarkers and the prediction of knee osteoarthritis 16 years after anterior cruciate ligament injury. Osteoarthritis Cartilage. Apr 2017;25(4):492–498.
   PubMed Web of Science ®Google Scholar
• Yu LP Jr.Jr., Smith GN Jr.Jr., Brandt KD, et al. Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis Rheum. Oct 1992;35(10):1150–1159.
   PubMedGoogle Scholar
• McNamara PS, Johnston SA, Todhunter RJ. Slow-acting, disease-modifying osteoarthritis agents. Vet Clin North Am Small Anim Pract. 1997 Jul;27(4):863–881.
   PubMed Web of Science ®Google Scholar
• Lauhio A, Salo T, Ding Y, et al. In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and non-steroidal anti-inflammatory drugs (NSAID) in acute reactive arthritis. Clin Exp Immunol. Oct 1994;98(1):21–28.
   PubMed Web of Science ®Google Scholar
• Golub LM, Elburki MS, Walker C, et al. Non-antibacterial tetracycline formulations: host-modulators in the treatment of periodontitis and relevant systemic diseases. Int Dent J. 2016 Jun;66(3):127–135.
   PubMed Web of Science ®Google Scholar
• Hanemaaijer R, Sorsa T, Konttinen YT, et al. Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells regulation by tumor necrosis factor-α and doxycycline. J Biol Chem. 1997;272(50):31504–31509.
   PubMed Web of Science ®Google Scholar
• Sorsa T, Golub LM. Is the excessive inhibition of matrix metalloproteinases (MMPs) by potent synthetic MMP inhibitors (MMPIs) desirable in periodontitis and other inflammatory diseases? That is: ‘Leaky’ MMPIs vs excessively efficient drugs. Oral Dis. 2005 Nov;11(6):408–409.
   PubMed Web of Science ®Google Scholar
• Gu Y, Lee HM, Sorsa T, et al. Non-antibacterial tetracyclines modulate mediators of periodontitis and atherosclerotic cardiovascular disease: a mechanistic link between local and systemic inflammation. Pharmacol Res. Dec 2011;64(6):573–579.
   PubMed Web of Science ®Google Scholar
• Brandt KD, Mazzuca SA, Katz BP, et al. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. Jul 2005;52(7):2015–2025.
   PubMed Web of Science ®Google Scholar
• Da Costa BR, Nuesch E, Reichenbach S, et al. Doxycycline for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. [2012 Nov 14];11:CD007323.
   PubMedGoogle Scholar
• Miller RE, Miller RJ, Malfait AM. Osteoarthritis joint pain: the cytokine connection. Cytokine. 2014 Dec;70(2):185–193.
   PubMed Web of Science ®Google Scholar
• Chevalier X, Eymard F, Richette P. Biologic agents in osteoarthritis: hopes and disappointments. Nat Rev Rheumatol. 2013 Jul;9(7):400–410.
   PubMed Web of Science ®Google Scholar
• Settle S, Vickery L, Nemirovskiy O, et al. Cartilage degradation biomarkers predict efficacy of a novel, highly selective matrix metalloproteinase 13 inhibitor in a dog model of osteoarthritis: confirmation by multivariate analysis that modulation of type II collagen and aggrecan degradation peptides parallels pathologic changes. Arthritis Rheum. 2010 Oct;62(10):3006–3015.
   PubMed Web of Science ®Google Scholar
• Cai H, Agrawal AK, Putt DA, et al. Assessment of the renal toxicity of novel anti-inflammatory compounds using cynomolgus monkey and human kidney cells. Toxicology. [2009 Apr 5];258(1):56–63.
   PubMed Web of Science ®Google Scholar
• Baragi VM, Becher G, Bendele AM, et al. A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models. Arthritis Rheum. Jul 2009;60(7):2008–2018.
   PubMed Web of Science ®Google Scholar
• Blagg JA, Noe MC, Wolf-Gouveia LA, et al. Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14. Bioorg Med Chem Lett. [2005 Apr 1];15(7):1807–1810.
   PubMed Web of Science ®Google Scholar
• Chen JM, Nelson FC, Levin JI, et al. Structure-based design of a novel, potent, and selective inhibitor for MMP-13 utilizing NMR spectroscopy and computer-aided molecular design. J Am Chem Soc. 2000;122(40):9648–9654.
   Web of Science ®Google Scholar
• Engel CK, Pirard B, Schimanski S, et al. Structural basis for the highly selective inhibition of MMP-13. Chem Biol. Feb 2005;12(2):181–189.
   PubMedGoogle Scholar
• Gao DA, Xiong Z, Heim-Riether A, et al. SAR studies of non-zinc-chelating MMP-13 inhibitors: improving selectivity and metabolic stability. Bioorg Med Chem Lett. [2010 Sep 1];20(17):5039–5043.
   PubMed Web of Science ®Google Scholar
• Gooljarsingh LT, Lakdawala A, Coppo F, et al. Characterization of an exosite binding inhibitor of matrix metalloproteinase 13. Protein Sci. Jan 2008;17(1):66–71.
   PubMed Web of Science ®Google Scholar
• Johnson AR, Pavlovsky AG, Ortwine DF, et al. Discovery and characterization of a novel inhibitor of matrix metalloproteinase-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J Biol Chem. [2007 Sep 21];282(38):27781–27791.
   PubMed Web of Science ®Google Scholar
• Jungel A, Ospelt C, Lesch M, et al. Effect of the oral application of a highly selective MMP-13 inhibitor in three different animal models of rheumatoid arthritis. Ann Rheum Dis. May 2010;69(5):898–902.
   PubMed Web of Science ®Google Scholar
• Lauer-Fields JL, Minond D, Chase PS, et al. High throughput screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-helical FRET substrate. Bioorg Med Chem. [2009 Feb 1];17(3):990–1005.
   PubMed Web of Science ®Google Scholar
• Piecha D, Weik J, Kheil H, et al. Novel selective MMP-13 inhibitors reduce collagen degradation in bovine articular and human osteoarthritis cartilage explants. Inflamm Res. May 2010;59(5):379–389.
   PubMed Web of Science ®Google Scholar
• Li JJ, Nahra J, Johnson AR, et al. Quinazolinones and pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. J Med Chem. [2008 Feb 28];51(4):835–841.
   PubMed Web of Science ®Google Scholar
• Reiter LA, Freeman-Cook KD, Jones CS, et al. Potent, selective pyrimidinetrione-based inhibitors of MMP-13. Bioorg Med Chem Lett. [2006 Nov 15];16(22):5822–5826.
   PubMed Web of Science ®Google Scholar
• Roth J, Minond D, Darout E, et al. Identification of novel, exosite-binding matrix metalloproteinase-13 inhibitor scaffolds. Bioorg Med Chem Lett. [2011 Dec 1];21(23):7180–7184.
   PubMed Web of Science ®Google Scholar
• Brown MT, Murphy FT, Radin DM, et al. Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial. Arthritis Rheum. Jul 2013;65(7):1795–1803.
   PubMedGoogle Scholar
• Barreto G, Soininen A, Ylinen P, et al. Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis. Arthritis Res Ther. [2015 Dec 24]; 17(1):379.
   PubMedGoogle Scholar
• Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013 Jan;21(1):16–21.
   PubMed Web of Science ®Google Scholar
• Greenwald RA. Thirty-six years in the clinical without an MMP inhibitor. What hath collagenase wrought? Ann N Y Acad Sci. [1999 Jun 30]; 878(1 INHIBITION OF):413–419.
   PubMedGoogle Scholar
• Lindy O, Konttinen YT, Sorsa T, et al. Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium. Arthritis Rheum. 1997;40(8):1391–1399.
   PubMedGoogle Scholar
• Murphy G, Nagase H. Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin Pract Rheumatol. 2008;4(3):128–135.
   PubMedGoogle Scholar
• Yamamoto K, Okano H, Miyagawa W, et al. MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1. Matrix Biol. 2016;56:57–73.
   PubMed Web of Science ®Google Scholar
• Fernandes JC, Martel-Pelletier J, Lascau-Coman V, et al. Collagenase-1 and collagenase-3 synthesis in normal and early experimental osteoarthritic canine cartilage: an immunohistochemical study. J Rheumatol. 1998 Aug;25(8):1585–1594.
   PubMed Web of Science ®Google Scholar
• Moldovan F, Pelletier JP, Hambor J, et al. Collagenase-3 (matrix metalloproteinase 13) is preferentially localized in the deep layer of human arthritic cartilage in situ: in vitro mimicking effect by transforming growth factor beta. Arthritis Rheum. Sep 1997;40(9):1653–1661.
   PubMed Web of Science ®Google Scholar
• Rydziel S, Delany AM, Canalis E. AU-rich elements in the collagenase 3 mRNA mediate stabilization of the transcript by cortisol in osteoblasts. J Biol Chem. 2004;279(7):5397–5404.
   PubMed Web of Science ®Google Scholar
• Xu N, Zhang L, Meisgen F, et al. MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. J Biol Chem. 2012;287(35):29899–29908.
   PubMed Web of Science ®Google Scholar
• Knäuper V, Will H, López-Otin C, et al. Cellular mechanisms for human procollagenase-3 (MMP-13) activation Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem. 1996;271(29):17124–17131.
   PubMed Web of Science ®Google Scholar
• Knäuper V, López-Otin C, Smith B, et al. Biochemical characterization of human collagenase-3. J Biol Chem. 1996;271(3):1544–1550.
   PubMed Web of Science ®Google Scholar
• Chan CM, Macdonald CD, Litherland GJ, et al. Cytokine-induced MMP13 expression in human chondrocytes is dependent on activating transcription factor 3 (Atf3) regulation. J Biol Chem. [2017 Feb 3];292(5):1625–1636.
   PubMed Web of Science ®Google Scholar
• Mengshol JA, Mix KS, Brinckerhoff CE. Matrix metalloproteinases as therapeutic targets in arthritic diseases: bull’s-eye or missing the mark? Arthritis Rheum. 2002 Jan;46(1):13–20.
   PubMedGoogle Scholar
• Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14(1):397–440.
   PubMed Web of Science ®Google Scholar
• Conaghan PG, Bowes MA, Kingsbury SR, et al. Disease-Modifying effects of a novel cathepsin k inhibitor in osteoarthritis: a randomized controlled trial. Ann Intern Med. [2020 Jan 21];172(2):86–95.
   PubMed Web of Science ®Google Scholar