Osteochondrosis in horses: An overview of genetic and other factors.

1. Edmonds EW, Shea KG. Osteochondritis dissecans: editorial comment.. Clin Orthop Relat Res 2013;471:1105–1106.
2. Bourebaba L, Röcken M, Marycz K. Osteochondritis dissecans (OCD) in horses – molecular background of its pathogenesis and perspectives for progenitor stem cell therapy.. Stem Cell Rev Rep 2019;15:374–390.
3. Ytrehus B, Carlson CS, Ekman S. Etiology and pathogenesis of osteochondrosis.. Vet Pathol 2007;44:429–448.
4. Chau MM, Klimstra MA, Wise KL, Ellermann JM, Tóth F, Carlson CS. Osteochondritis dissecans: current understanding of epidemiology, etiology, management, and outcomes.. J Bone Joint Surg Am 2021;103:1132–1151.
5. Vezzoni A, Benjamino K. Canine elbow dysplasia: ununited anconeal process, osteochondritis dissecans, and medial coronoid process disease.. Vet Clin North Am Small Anim Pract 2021;51:439–474.
6. Finnøy A, Olstad K, Lilledahl MB. Characterization of cellular and matrix alterations in the early pathogenesis of osteochondritis dissecans in pigs using second harmonic generation and two‐photon excitation fluorescence microscopy.. J Orthop Res 2018;36:2089–2098.
7. Reiland S, Strömberg B, Olsson SE, Dreimanis I, Olsson IG. Osteochondrosis in growing bulls. Pathology, frequency and severity on different feedings.. Acta Radiol Suppl 1978;358:179–196.
8. Poulos PW. Tibial dyschondroplasia (osteochondrosis) in the Turkey. A morphologic investigation.. Acta Radiol Suppl 1978;358:197–227.
9. Poulos PW, Reiland S, Elwinger K, Olsson SE. Skeletal lesions in the broiler, with special reference to dyschondroplasia (osteochondrosis). Pathology, frequency and clinical significance in two strains of birds on high and low energy feed.. Acta Radiol Suppl 1978;358:229–275.
10. Rejnö S, Strömberg B. Osteochondrosis in the horse. II. Pathology.. Acta Radiol Suppl 1978;358:153–178.
11. Janutta V, Distl O. Review on canine elbow dysplasia: pathogenesis, diagnosis, prevalence and genetic aspects.. Dtsch Tierarztl Wochenschr 2008;115:172–181.
12. Jørgensen B. Osteochondrosis/osteoarthrosis and claw disorders in sows, associated with leg weakness.. Acta Vet Scand 2000;41:123–138.
13. Carlson CS, Cullins LD, Meuten DJ. Osteochondrosis of the articular‐epiphyseal cartilage complex in young horses: evidence for a defect in cartilage canal blood supply.. Vet Pathol 1995;32:641–647.
14. de Grauw JC, Brama PA, Wiemer P, Brommer H, van de Lest CH, van Weeren PR. Cartilage‐derived biomarkers and lipid mediators of inflammation in horses with osteochondritis dissecans of the distal intermediate ridge of the tibia.. Am J Vet Res 2006;67:1156–1162.
15. Firth EC, van Weeren PR, Pfeiffer DU, Delahunt J, Barneveld A. Effect of age, exercise and growth rate on bone mineral density (BMD) in third carpal bone and distal radius of Dutch Warmblood foals with osteochondrosis.. Equine Vet J 1999;31(S31):74–78.
16. Jeffcott LB, Henson FMD. Studies on growth cartilage in the horse and their application to aetiopathogenesis of dyschondroplasia (osteochondrosis).. Vet J 1998;156:177–192.
17. Donabédian M, van Weeren PR, Perona G, Fleurance G, Robert C, Léger S. Early changes in biomarkers of skeletal metabolism and their association to the occurrence of osteochondrosis (OC) in the horse.. Equine Vet J 2008;40:253–259.
18. Olstad K, Ytrehus B, Ekman S, Carlson CS, Dolvik NI. Early lesions of osteochondrosis in the distal femur of foals.. J Orthop Res 2008;26(2):286–293.
19. Stuart PR, Brantigan JW. Osteochondritis dissecans of the spine: a report of three cases and a review of the literature.. Spine (Phila Pa 1976) 1997;22(10):1150–1155.
20. Olstad K, Ekman S, Carlson CS, Ytrehus B. An update on the pathogenesis of osteochondrosis.. Vet Pathol 2011;48(1):1–17.
21. Jeffcott LB. Osteochondrosis in the horse—searching for the key to pathogenesis.. Equine Vet J 1991;23(5):331–338.
22. Barneveld A, van Weeren PR. Diagnosis and prediction of osteochondrosis in the horse.. Vet Clin North Am Equine Pract 1999;15(1):25–42.
23. Bruns J, Werner M, Habermann CR. Osteochondritis dissecans of smaller joints: the elbow.. Cartilage 2021;12:407–417.
24. Pascual‐Garrido C, Moran CJ, Green DW, Cole BJ. Osteochondritis dissecans of the knee in children and adolescents.. Curr Opin Pediatr 2013;25:46–51.
25. Bruns J, Werner M, Habermann C. Osteochondritis dissecans: etiology, pathology, and imaging with a special focus on the knee joint.. Cartilage 2018;9:346–362.
26. Schenck RC, Goodnight JM. Osteochondritis dissecans.. J Bone Joint Surg Am 1996;78:439–456.
27. Mcllwraith CW. Clinical aspects of osteochondritis dissecans.. In: Mcllwraith CW, Trotter GW, editors. Joint disease in the horse. Philadelphia: WB Saunders Co; 1996. p. 369–374.
28. Ramos S, Pinto A, Crespo J, Marques JP, Bettencourt E, Gama LT. Osteochondrosis (osteochondritis dissecans) in Lusitano horses: prevalence and characteristics.. J Equine Vet Sci 2022;117:104063.
29. Mendoza L, Lejeune JP, Caudron I, Detilleux J, Sandersen C, Deliège B. Impact of feeding and housing on the development of osteochondrosis in foals—a longitudinal study.. Prev Vet Med 2016;127:10–14.
30. Denoix JM, Jacquet S, Lepeule J, Crevier‐Denoix N, Valette J‐P, Robert C. Radiographic findings of juvenile osteochondral conditions detected in 392 foals using a field radiographic protocol.. Vet J 2013;197:44–51.
31. Santschi EM, Prichard MA, Whitman JL, Batten CA, Strathman TA, Canada NC. Stifle radiography in thoroughbreds from 6 to 8 months of age.. Equine Vet Educ 2020;32:78–84.
32. Grondalen T. Osteochondrosis and arthrosis in pigs. 3. A comparison of the incidence in young animals of the Norwegian Landrace and Yorkshire breeds.. Acta Vet Scand 1974;15:43–52.
33. Grondalen T. Osteochondrosis and arthrosis in pigs. VII. Relationship to joint shape and exterior conformation.. Acta Vet Scand Suppl 1974;46:1–32.
34. Grondalen T. Leg weakness in pigs. II. Litter differences in leg weakness, skeletal lesions, joint shape and exterior conformation.. Acta Vet Scand 1974;15:574–586.
35. Olstad K, Ekman S, Carlson CS. An update on the pathogenesis of osteochondrosis.. Vet Pathol 2015;52:785–802.
36. Schoenmakers I, Hazewinkel HA, Voorhout G, Carlson CS, Richardson D. Effects of diets with different calcium and phosphorus contents on the skeletal development and blood chemistry of growing great danes.. Vet Rec 2000;147(23):652–660.
37. Shingleton WD, Mackie EJ, Cawston TE, Jeffcott LB. Cartilage canals in equine articular/epiphyseal growth cartilage and a possible association with dyschondroplasia.. Equine Vet J 1997;29(5):360–364.
38. Grez‐Capdeville M, Gross N, Baker JC, Shutter JA, Haas AR, Wilson ME. Alleged predisposing dietary factors fail to increase the incidence of osteochondrosis‐like lesions in growing pigs at 14 and 24 wk of age.. J Anim Sci 2020;98(4):skaa103.
39. Richardson DC, Zentek J. Nutrition and osteochondrosis.. Vet Clin North Am Small Anim Pract 1998;28(1):115–135.
40. Gee E, Davies M, Firth E, Jeffcott L, Fennessy P, Mogg T. Osteochondrosis and copper: histology of articular cartilage from foals out of copper supplemented and non‐supplemented dams.. Vet J 2007;173(1):109–117.
41. Billinghurst RC, Brama PAJ, van Weeren PR, Knowlton MS, McIlwraith CW. Significant exercise‐related changes in the serum levels of two biomarkers of collagen metabolism in young horses.. Osteoarthr Cartil 2003;11(10):760–769.
    doi: 10.1016/s1063-4584(03)00152-3google scholar: lookup
42. Firth EC. The response of bone, articular cartilage and tendon to exercise in the horse.. J Anat 2006;208:513–526.
43. Bates JT, Jacobs JC, Shea KG, Oxford JT. Emerging genetic basis of osteochondritis dissecans.. Clin Sports Med 2014;33:199–220.
44. Masquijo J, Kothari A. Juvenile osteochondritis dissecans (JOCD) of the knee: current concepts review.. EFORT Open Rev 2019;4(5):201–212.
45. Andriolo L, Crawford DC, Reale D, Zaffagnini S, Candrian C, Cavicchioli A. Osteochondritis dissecans of the knee: etiology and pathogenetic mechanisms. A systematic review.. Cartilage 2020;11(3):273–290.
46. Grøndalen T, Vangen O. Osteochondrosis and arthrosis in pigs.. Acta Vet Scand 1974;15:61–79.
47. Grondalen T, Grondalen J. Osteochondrosis and arthrosis in pigs. IV. Effect of overloading on the distal epiphyseal plate of the ulna.. Acta Vet Scand 1974;15(1):53–60.
48. Stoeckl BD, Zlotnick HM, Farrell MJ, Fryhofer GW, Hast MW, Miller LM. The porcine accessory carpal bone as a model for biologic joint replacement for trapeziometacarpal osteoarthritis.. Acta Biomater 2021;129:159–168.
49. Dierks C, Löhring K, Lampe V, Wittwer C, Drögemüller C, Distl O. Genome‐wide search for markers associated with osteochondrosis in Hanoverian warmblood horses.. Mamm Genome 2007;18:739–747.
50. Dierks C, Komm K, Lampe V, Distl O. Fine mapping of a quantitative trait locus for osteochondrosis on horse chromosome 2.. Anim Genet 2010;41:87–90.
51. Lampe V, Dierks C, Distl O. Refinement of a quantitative trait locus on equine chromosome 5 responsible for fetlock osteochondrosis in Hanoverian warmblood horses.. Anim Genet 2009;40:553–555.
52. Lampe V, Dierks C, Distl O. Refinement of a quantitative gene locus on equine chromosome 16 responsible for osteochondrosis in Hanoverian warmblood horses.. Animal 2009;3:1224–1231.
53. Lampe V, Dierks C, Komm K, Distl O. Identification of a new quantitative trait locus on equine chromosome 18 responsible for osteochondrosis in Hanoverian warmblood horses.. J Anim Sci 2009;87:3477–3481.
54. Wittwer C, Dierks C, Hamann H, Distl O. Associations between candidate gene markers at a quantitative trait locus on equine chromosome 4 responsible for osteochondrosis dissecans in fetlock joints of south German Coldblood horses.. J Hered 2008;99:125–129.
55. Wittwer C, Löhring K, Drögemüller C, Hamann H, Rosenberger E, Distl O. Mapping quantitative trait loci for osteochondrosis in fetlock and hock joints and palmar/plantar osseus fragments in fetlock joints of South German Coldblood horses.. Anim Genet 2007;38:350–357.
56. Wittwer C, Hamann H, Distl O. The candidate gene XIRP2 at a quantitative gene locus on equine chromosome 18 associated with osteochondrosis in fetlock and hock joints of South German Coldblood horses.. J Hered 2009;100:481–486.
57. Corbin LJ, Blott SC, Swinburne JE, Sibbons C, Fox‐Clipsham LY, Helwegen M. A genome‐wide association study of osteochondritis dissecans in the thoroughbred.. Mamm Genome 2012;23(3‐4):294–303.
    doi: 10.1007/s00335-011-9363-1google scholar: lookup
58. Lykkjen S, Dolvik NI, McCue ME, Rendahl AK, Mickelson JR, Roed KH. Genome‐wide association analysis of osteochondrosis of the tibiotarsal joint in Norwegian standardbred trotters.. Anim Genet 2010;41:111–120.
59. Selvaraj V, Sekaran S, Dhanasekaran A, Warrier S. Type 1 collagen: synthesis, structure and key functions in bone mineralization.. Differentiation 2024;136:100757.
60. Li S, Wang H, Zhang Y, Qiao R, Xia P, Kong Z. COL3A1 and MMP9 serve as potential diagnostic biomarkers of osteoarthritis and are associated with immune cell infiltration.. Front Genet 2021;12:721258.
61. Palomino Lago E, Baird A, Blott SC, McPhail RE, Ross AC, Durward‐Akhurst SA. A functional single‐nucleotide polymorphism upstream of the collagen type III gene is associated with catastrophic fracture risk in thoroughbred horses.. Animals Basel 2023;14(1):116.
62. Mak KM, Png CYM, Lee DJ. Type V collagen in health, disease, and fibrosis.. Anat Rec 2016;299:613–629.
63. Xu W‐B, Kotheeranurak V, Zhang H‐L, Feng J‐Y, Liu J‐W, Chen C‐M. Identification of the circRNA–miRNA–mRNA regulatory network in osteoarthritis using bioinformatics analysis.. Front Genet 2022;13:994163.
64. Emanuel BS, Cannizzaro LA, Seyer JM, Myers JC. Human alpha 1(III) and alpha 2(V) procollagen genes are located on the long arm of chromosome 2.. Proc Natl Acad Sci U S A 1985;82:3385–3389.
65. Watanabe M, Nakagawa R, Naruto T, Kohmoto T, Suga K, Goji A. A novel missense mutation of COL5A2 in a patient with Ehlers–Danlos syndrome.. Hum Genome Var 2016;3:16030.
66. Chiarelli N, Carini G, Zoppi N, Ritelli M, Colombi M. Molecular insights in the pathogenesis of classical Ehlers‐Danlos syndrome from transcriptome‐wide expression profiling of patients' skin fibroblasts.. PLoS One 2019;14:e0211647.
67. Wypchło M, Korwin‐Kossakowska A, Bereznowski A, Hecold M, Lewczuk D. Polymorphisms in selected genes and analysis of their relationship with osteochondrosis in Polish sport horse breeds.. Anim Genet 2018;49:623–627.
68. Pace JM, Corrado M, Missero C, Byers PH. Identification, characterization and expression analysis of a new fibrillar collagen gene, COL27A1.. Matrix Biol 2003;22:3–14.
69. Yau MS, Yerges‐Armstrong LM, Liu Y, Lewis CE, Duggan DJ, Renner JB. Genome‐wide association study of radiographic knee osteoarthritis in north American Caucasians.. Arthritis Rheumatol 2017;69(2):343–351.
    doi: 10.1002/art.39932google scholar: lookup
70. Rai MF, Tycksen ED, Cai L, Yu J, Wright RW, Brophy RH. Distinct degenerative phenotype of articular cartilage from knees with meniscus tear compared to knees with osteoarthritis.. Osteoarthr Cartil 2019;27:945–955.
71. Sevane N, Dunner S, Boado A, Cañon J. Polymorphisms in ten candidate genes are associated with conformational and locomotive traits in Spanish Purebred horses.. J Appl Genet 2017;58:355–361.
72. Koch M, Laub F, Zhou P, Hahn RA, Tanaka S, Burgeson RE. Collagen XXIV, a vertebrate fibrillar collagen with structural features of invertebrate collagens: selective expression in developing cornea and bone.. J Biol Chem 2003;278:43236–43244.
73. Halper J, Kjaer M. Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins.. Adv Exp Med Biol 2014;802:31–47.
74. Tzu J, Marinkovich MP. Bridging structure with function: structural, regulatory, and developmental role of laminins.. Int J Biochem Cell Biol 2008;40:199–214.
75. Kruegel J, Miosge N. Basement membrane components are key players in specialized extracellular matrices.. Cell Mol Life Sci 2010;67:2879–2895.
76. Foldager CB, Toh WS, Gomoll AH, Olsen BR, Spector M. Distribution of basement membrane molecules, laminin and collagen type IV, in normal and degenerated cartilage tissues.. Cartilage 2014;5:123–132.
77. Foldager CB, Toh WS, Christensen BB, Lind M, Gomoll AH, Spector M. Collagen type IV and laminin expressions during cartilage repair and in late clinically failed repair tissues from human subjects.. Cartilage 2016;7:52–61.
78. Alexopoulos LG, Williams GM, Upton ML, Setton LA, Guilak F. Osteoarthritic changes in the biphasic mechanical properties of the chondrocyte pericellular matrix in articular cartilage.. J Biomech 2005;38:509–517.
79. Azarpeykan S, Dittmer KE, Gee EK, Marshall JC, Wallace J, Elder P. Influence of blanketing and season on vitamin D and parathyroid hormone, calcium, phosphorus, and magnesium concentrations in horses in New Zealand.. Dom Anim Endocrinol 2016;56:75–84.
80. Kumar R, Thompson JR. The regulation of parathyroid hormone secretion and synthesis.. J Am Soc Nephrol 2011;22:216–224.
81. Rhee Y, Allen MR, Condon K, Lezcano V, Ronda AC, Galli C. PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling.. J Bone Miner Res 2011;26:1035–1046.
82. Calvi LM, Schipani E. The PTH/PTHrP receptor in Jansen's metaphyseal chondrodysplasia.. J Endocrinol Invest 2000;23(8):545–554.
83. Orth P, Cucchiarini M, Zurakowski D, Menger MD, Kohn DM, Madry H. Parathyroid hormone [1‐34] improves articular cartilage surface architecture and integration and subchondral bone reconstitution in osteochondral defects in vivo.. Osteoarthr Cartil 2013;21:614–624.
84. Beena S, Murlidhar L, Seshadri S, Jagadeesh S, Suresh I. Usefulness of fetal autopsy in the diagnosis of blomstrand chondrodysplasia: a report of three cases.. J Matern Fetal Neonatal Med 2017;30:1041–1044.
85. Matsuo N, Tanaka S, Yoshioka H, Koch M, Gordon MK, Ramirez F. Collagen XXIV (Col24a1) gene expression is a specific marker of osteoblast differentiation and bone formation.. Connect Tissue Res 2008;49:68–75.
86. Collinson M, Leonard SJ, Charlton J, Crolla JA, Silve C, Hall CM. Symmetrical enchondromatosis is associated with duplication of 12p11.23 to 12p11.22 including PTHLH.. Am J Med Genet A 2010;152A:3124–3128.
87. Schipani E, Provot S. PTHrP, PTH, and the PTH/PTHrP receptor in endochondral bone development.. Birth Defects Res C Embryo Today 2003;69(4):352–362.
88. Fradinho MJ, Mateus L, Bernardes N, Bessa RJB, Caldeira RM, Ferreira‐Dias G. Growth patterns, metabolic indicators and osteoarticular status in the Lusitano horse: a longitudinal study.. PLoS One 2019;14:e0219900.
89. van Oldruitenborgh‐Oosterbaan MMS, Mol JA, Barneveld A. Hormones, growth factors and other plasma variables in relation to osteochondrosis.. Equine Vet J 1999;31:45–54.
90. Adams AE, Rosenblatt M, Suva LJ. Identification of a novel parathyroid hormone‐responsive gene in human osteoblastic cells.. Bone 1999;24:305–313.
91. Khundmiri SJ, Murray RD, Lederer E. PTH and vitamin D.. Compreh Physiol 2016;6:561–601.
92. Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor.. Endocrinology 2006;147:5542–5548.
93. DeMambro VE, Tian L, Karthik V, Rosen CJ, Guntur AR. Effects of PTH on osteoblast bioenergetics in response to glucose.. Bone Rep 2023;19:101705.
94. Esbrit P, Alcaraz MJ. Current perspectives on parathyroid hormone (PTH) and PTH‐related protein (PTHrP) as bone anabolic therapies.. Biochem Pharmacol 2013;85:1417–1423.
95. Meulenbelt I, Min JL, van Duijn CM, Kloppenburg M, Breedveld FC, Slagboom PE. Strong linkage on 2q33.3 to familial early‐onset generalized osteoarthritis and a consideration of two positional candidate genes.. Eur J Hum Genet 2006;14:1280–1287.
96. Serteyn D, Piquemal D, Vanderheyden L, Lejeune J‐P, Verwilghen D, Sandersen C. Gene expression profiling from leukocytes of horses affected by osteochondrosis.. J Orthop Res 2010;28:965–970.
97. Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH‐related protein.. Science 1996;273:613–622.
98. Riddick TL, Duesterdieck‐Zellmer K, Semevolos SA. Gene and protein expression of cartilage canal and osteochondral junction chondrocytes and full‐thickness cartilage in early equine osteochondrosis.. Vet J 2012;194:319–325.
99. Semevolos SA, Brower‐Toland BD, Bent SJ, Nixon AJ. Parathyroid hormone‐related peptide and Indian hedgehog expression patterns in naturally acquired equine osteochondrosis.. J Orthop Res 2002;20:1290–1297.
100. Sassi N, Laadhar L, Allouche M, Achek A, Kallel‐Sellami M, Makni S. WNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology.. J Recept Signal Transduct 2014;34:73–80.
101. Tamamura Y, Otani T, Kanatani N, Koyama E, Kitagaki J, Komori T. Developmental regulation of Wnt/β‐catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification.. J Biol Chem 2005;280:19185–19195.
102. Luyten FP, Tylzanowski P, Lories RJ. Wnt signaling and osteoarthritis.. Bone 2009;44:522–527.
103. Corr M. Wnt‐β‐catenin signaling in the pathogenesis of osteoarthritis.. Nat Rev Rheumatol 2008;4:550–556.
104. Kinsley MA, Semevolos SA, Duesterdieck‐Zellmer KF. Wnt/β‐catenin signaling of cartilage canal and osteochondral junction chondrocytes and full thickness cartilage in early equine osteochondrosis.. J Orthop Res 2015;33:1433–1438.
105. Marchant EA, Semevolos SA. Differential protein expression of the marginal transitional zone in foals with osteochondrosis.. J Equine Vet Sci 2022;116:104055.
106. Russo AF. Calcitonin gene‐related peptide (CGRP).. Annu Rev Pharmacol Toxicol 2015;55:533–552.
107. Stöckl S, Eitner A, Bauer RJ, König M, Johnstone B, Grässel S. Substance P and alpha‐calcitonin gene‐related peptide differentially affect human osteoarthritic and healthy chondrocytes.. Front Immunol 2021;12:722884.
108. Wang Q, Qin H, Deng J, Xu H, Liu S, Weng J. Research progress in calcitonin gene‐related peptide and bone repair.. Biomolecules 2023;13:838.
109. Powell R, Young VA, Pryce KD, Sheehan GD, Bonsu K, Ahmed A. Inhibiting endocytosis in CGRP+ nociceptors attenuates inflammatory pain‐like behavior.. Nat Commun 2021;12:5812.
110. Yu H, Huang T, Lu WW, Tong L, Chen D. Osteoarthritis pain.. Int J Mol Sci 2022;23:4642.
111. Bigal ME, Edvinsson L, Rapoport AM, Lipton RB, Spierings ELH, Diener H‐C. Safety, tolerability, and efficacy of TEV‐48125 for preventive treatment of chronic migraine: a multicentre, randomised, double‐blind, placebo‐controlled, phase 2b study.. Lancet Neurol 2015;14:1091–1100.
112. Edvinsson L. CGRP blockers in migraine therapy: where do they act?. Br J Pharmacol 2009;155(7):967–969.
113. Hoang B, Moos M, Vukicevic S, Luyten FP. Primary structure and tissue distribution of FRZB, a novel protein related to drosophila frizzled, suggest a role in skeletal morphogenesis.. J Biol Chem 1996;271(42):26131–26137.
     doi: 10.1074/jbc.271.42.26131google scholar: lookup
114. Yagi H, Takahata Y, Murakami T, Nakaminami Y, Hagino H, Yamamoto S. Transcriptional regulation of FRZB in chondrocytes by Osterix and Msx2.. J Bone Miner Metab 2022;40:723–734.
115. Loughlin J, Dowling B, Chapman K, Marcelline L, Mustafa Z, Southam L. Functional variants within the secreted frizzled‐related protein 3 gene are associated with hip osteoarthritis in females.. Proc Natl Acad Sci U S A 2004;101:9757–9762.
116. Lories RJU, Peeters J, Bakker A, Tylzanowski P, Derese I, Schrooten J. Articular cartilage and biomechanical properties of the long bones in Frzb‐knockout mice.. Arthritis Rheumatol 2007;56(12):4095–4103.
     doi: 10.1002/art.23137google scholar: lookup
117. Mukherjee A, Das B. The role of inflammatory mediators and matrix metalloproteinases (MMPs) in the progression of osteoarthritis.. Biomater Biosyst 2024;13:100090.
118. Naccache F, Metzger J, Distl O. Genetic risk factors for osteochondrosis in various horse breeds.. Equine Vet J 2018;50:556–563.
119. Inada M, Wang Y, Byrne MH, Rahman MU, Miyaura C, López‐Otín C. Critical roles for collagenase‐3 (Mmp13) in development of growth plate cartilage and in endochondral ossification.. Proc Natl Acad Sci U S A 2004;101:17192–17197.
120. Mirams M, Tatarczuch L, Ahmed YA, Pagel CN, Jeffcott LB, Davies HMS. Altered gene expression in early osteochondrosis lesions.. J Orthop Res 2009;27:452–457.
121. Komori T. Runx2, a multifunctional transcription factor in skeletal development.. J Cell Biochem 2002;87:1–8.
122. Enomoto H, Enomoto‐Iwamoto M, Iwamoto M, Nomura S, Himeno M, Kitamura Y. Cbfa1 is a positive regulatory factor in chondrocyte maturation.. J Biol Chem 2000;275:8695–8702.
123. van de Lest CHA, Brama PAJ, van El B, DeGroot J, van Weeren PR. Extracellular matrix changes in early osteochondrotic defects in foals: a key role for collagen?. Biochim Biophys Acta Mol Basis Dis 2004;1690:54–62.
124. Ronzière M‐C, Aubert‐Foucher E, Gouttenoire J, Bernaud J, Herbage D, Mallein‐Gerin F. Integrin α1β1 mediates collagen induction of MMP‐13 expression in MC615 chondrocytes.. Biochim Biophys Acta Mol Cell Res 2005;1746:55–64.
125. Yoshida CA, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog.. Genes Dev 2004;18:952–963.
126. Zelzer E, Glotzer DJ, Hartmann C, Thomas D, Fukai N, Soker S. Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2.. Mech Dev 2001;106:97–106.
127. Paulsson M, Heinegård D. Matrix proteins bound to associatively prepared proteoglycans from bovine cartilage.. Biochem J 1979;183:539–545.
128. Paulsson M, Wagener R. Chapter 23 – Matrilins.. In: Mecham RP, editor. Methods in cell biology. St. Louis, MO: Academic Press; 2018. p. 429–446.
129. Rodrigues JB, Araújo S, Guedes‐Pinto H, San Roman F, Viegas C, Bastos E. Analysis of new Matrilin‐1 gene variants in a case‐control study related to dental malocclusions in Equus asinus.. Gene 2013;522:70–74.
130. Deák F, Wagener R, Kiss I, Paulsson M. The matrilins: a novel family of oligomeric extracellular matrix proteins.. Matrix Biol 1999;18:55–64.
131. Chen Y, Cossman J, Jayasuriya CT, Li X, Guan Y, Fonseca V. Deficient mechanical activation of anabolic transcripts and post‐traumatic cartilage degeneration in Matrilin‐1 knockout mice.. PLoS One 2016;11:e0156676.
132. Triggs‐Raine B, Salo TJ, Zhang H, Wicklow BA, Natowicz MR. Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX.. Proc Natl Acad Sci U S A 1999;96:6296–6300.
133. Natowicz MR, Short MP, Wang Y, Dickersin GR, Gebhardt MC, Rosenthal DI. Clinical and biochemical manifestations of hyaluronidase deficiency.. N Engl J Med 1996;335:1029–1033.
134. Jung H. Hyaluronidase: an overview of its properties, applications, and side effects.. Arch Plast Surg 2020;47:297–300.
135. Wang T‐P, Pan Y‐R, Fu C‐Y, Chang H‐Y. Down‐regulation of UDP‐glucose dehydrogenase affects glycosaminoglycans synthesis and motility in HCT‐8 colorectal carcinoma cells.. Exp Cell Res 2010;316:2893–2902.
136. Caon I, Parnigoni A, Viola M, Karousou E, Passi A, Vigetti D. Cell energy metabolism and hyaluronan synthesis.. J Histochem Cytochem 2021;69:35–47.
137. Machado TSL, Correia da Silva LCL, Baccarin RYA, Michelacci YM. Synovial fluid chondroitin sulphate indicates abnormal joint metabolism in asymptomatic osteochondritic horses.. Equine Vet J 2012;44:404–411.
138. Wen Y, Li J, Wang L, Tie K, Magdalou J, Chen L. UDP‐glucose dehydrogenase modulates proteoglycan synthesis in articular chondrocytes: its possible involvement and regulation in osteoarthritis.. Arth Res Ther 2014;16:484.
139. Austbø L, Røed KH, Dolvik NI, Skretting G. Identification of differentially expressed genes associated with osteochondrosis in standardbred horses using RNA arbitrarily primed PCR.. Anim Biotechnol 2010;21:135–139.
140. Billinghurst RC, Brama PAJ, van Weeren PR, Knowlton MS, McIlwraith CW. Evaluation of serum concentrations of biomarkers of skeletal metabolism and results of radiography as indicators of severity of osteochondrosis in foals.. Am J Vet Res 2004;65(2):143–150.
     doi: 10.2460/ajvr.2004.65.143google scholar: lookup
141. Ishizuka Y, Mochizuki R, Yanai K, Takatsuka M, Nonomura T, Niida S. Induction of hydroxyapatite resorptive activity in bone marrow cell populations resistant to bafilomycin A1 by a factor with restricted expression to bone and brain, neurochondrin.. Biochim Biophys Acta Mol Cell Res 1999;1450:92–98.
142. Mochizuki R, Dateki M, Yanai K, Ishizuka Y, Amizuka N, Kawashima H. Targeted disruption of the neurochondrin/norbin gene results in embryonic lethality.. Biochem Biophys Res Commun 2003;310:1219–1226.
143. Groth A, Lukas J, Nigg EA, Silljé HHW, Wernstedt C, Bartek J. Human tousled like kinases are targeted by an ATM‐ and Chk1‐dependent DNA damage checkpoint.. EMBO J 2003;22:1676–1687.
144. Silljé HH, Takahashi K, Tanaka K, Van Houwe G, Nigg EA. Mammalian homologues of the plant Tousled gene code for cell‐cycle‐regulated kinases with maximal activities linked to ongoing DNA replication.. EMBO J 1999;18:5691–5702.
145. He S, Yang S, Zhang Y, Li X, Gao D, Zhong Y. LncRNA ODIR1 inhibits osteogenic differentiation of hUC‐MSCs through the FBXO25/H2BK120ub/H3K4me3/OSX axis.. Cell Death Dis 2019;10:947.
146. Cheng X, Song X, Li Z, Yuan C, Lei X, Feng M. Acyloxyacyl hydrolase deficiency induces chronic inflammation and bone loss in male mice.. J Mol Med 2022;100:1599–1616.
147. Roodman GD, Kurihara N, Ohsaki Y, Kukita A, Hosking D, Demulder A. Interleukin 6. A potential autocrine/paracrine factor in Paget's disease of bone.. J Clin Invest 1992;89:46–52.
148. Agreste FR, Moreira JJ, Fülber J, Bogossian PM, Chaible LM, Silva LCLC. Arthroscopic evaluation of the synovial membrane and its relationship with histological changes and biomarkers in equine joint disease.. Res Vet Sci 2021;140:212–220.
149. Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations.. Ther Adv Musculoskelet Dis 2013;5:77–94.
150. Gabay C. Interleukin‐6 and chronic inflammation.. Arthritis Res Ther 2006;8:S3.
151. Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez‐Reino JJ. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study.. Ann Rheum Dis 2010;69:88–96.
152. de Hooge ASK, van de Loo FAJ, Bennink MB, Arntz OJ, de Hooge P, van den Berg WB. Male IL‐6 gene knock out mice developed more advanced osteoarthritis upon aging.. Osteoarthr Cartil 2005;13:66–73.
153. Ley C, Ekman S, Elmén A, Nilsson G, Eloranta M‐L. Interleukin‐6 and tumour necrosis factor in synovial fluid from horses with carpal joint pathology.. J Vet Med A Physiol Pathol Clin Med 2007;54:346–351.
154. Liu AY, Gu D, Hixson JE, Rao DC, Shimmin LC, Jaquish CE. Genome‐wide linkage and regional association study of obesity‐related phenotypes: the GenSalt study.. Obesity (Silver Spring) 2014;22(2):545–556.
155. Novakofski KD, Torre CJ, Fortier LA. Interleukin‐1α, ‐6, and ‐8 decrease Cdc42 activity resulting in loss of articular chondrocyte phenotype.. J Orthop Res 2012;30:246–251.
156. Reesink HL, Nixon AJ, Su J, Liu S, Sutton RM, Mann S. Galectins‐1 and‐3 increase in equine post‐traumatic osteoarthritis.. Front Vet Sci 2018;5:288.
157. Ohshima S, Kuchen S, Seemayer CA, Kyburz D, Hirt A, Klinzing S. Galectin 3 and its binding protein in rheumatoid arthritis.. Arthritis Rheum 2003;48:2788–2795.
158. Forsman H, Islander U, Andréasson E, Andersson A, Onnheim K, Karlstrøm A. Galectin 3 aggravates joint inflammation and destruction in antigen‐induced arthritis.. Arthritis Rheum 2011;63(2):445–454.
159. Harjacek M, Diaz‐Cano S, De Miguel M, Wolfe H, Maldonado CA, Rabinovich GA. Expression of galectins‐1 and ‐3 correlates with defective mononuclear cell apoptosis in patients with juvenile idiopathic arthritis.. J Rheumatol 2001;28:1914–1922.
160. Reesink HL, Bonnevie ED, Liu S, Shurer CR, Hollander MJ, Bonassar LJ. Galectin‐3 binds to lubricin and reinforces the lubricating boundary layer of articular cartilage.. Sci Rep 2016;6:25463.
161. Olstad K, Ytrehus B, Ekman S, Carlson CS, Dolvik NI. Epiphyseal cartilage canal blood supply to the tarsus of foals and relationship to osteochondrosis.. Equine Vet J 2008;40:30–39.
162. Nishida Y, Nagata T, Takahashi Y, Sugahara‐Kobayashi M, Murata A, Asai S. Alteration of serum/glucocorticoid regulated kinase‐1 (sgk‐1) gene expression in rat hippocampus after transient global ischemia.. Mol Brain Res 2004;123:121–125.
163. Pacholsky D, Vakeel P, Himmel M, Löwe T, Stradal T, Rottner K. Xin repeats define a novel actin‐binding motif.. J Cell Sci 2004;117:5257–5268.
164. Hou T, Zhou L, Wang L, Kazobinka G, Zhang X, Chen Z. CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT pathway.. Oncotarget 2017;8:93001–93013.
165. Martinez‐Sanchez A, Dudek KA, Murphy CL. Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA‐145 (miRNA‐145).. J Biol Chem 2012;287:916–924.
166. Lykkjen S, Roed KH, Dolvik NI. Osteochondrosis and osteochondral fragments in Standardbred trotters: prevalence and relationships.. Equine Vet J 2012;44:332–338.
167. Hilla D, Distl O. Prevalence of osteochondral fragments, osteochondrosis dissecans and palmar/plantar osteochondral fragments in Hanoverian Warmblood horses.. Berl Munch Tierarztl Wochenschr 2013;126:236–244.
168. Wittwer C, Hamann H, Rosenberger E, Distl O. Prevalence of osteochondrosis in the limb joints of South German Coldblood horses.. J Vet Med A Physiol Pathol Clin Med 2006;53:531–539.
169. Jönsson L, Dalin G, Egenvall A, Näsholm A, Roepstorff L, Philipsson J. Equine hospital data as a source for study of prevalence and heritability of osteochondrosis and palmar/plantar osseous fragments of Swedish Warmblood horses.. Equine Vet J 2011;43:695–700.
170. Vos NJ. Incidence of osteochondrosis (dissecans) in Dutch warmblood horses presented for pre‐purchase examination.. Irish Vet J 2008;61:33–37.
171. Boado A, López‐Sanromán FJ. Prevalence and characteristics of osteochondrosis in 309 Spanish purebred horses.. Vet J 2015;207:112–117.
172. Valette J‐P, Denoix J‐M. Analyse retrospective des scores radiographiques des chevaux presentes aux concours d'achat des etalons nationaux entre 1996 et 2000.. Les Haras Nationaux 2001;27:147–153.
173. Van Cauter R, Caudron I, Lejeune J‐P, Rousset A, Serteyn D. Nineteen years of radiographic screening: impact of sepsis and evolution of osteochondrosis dissecans prevalence in Walloon sport horses born between 2004 and 2022.. PLoS One 2024;19:e0308304.
174. Maia MPM, Weber SH, Bastos LFC, Michelotto PV. Prevalence of juvenile osteochondral conditions in yearling thoroughbred racehorses in southern Brazil.. J Equine Vet Sci 2020;90:102997.

Citations