Changes of subchondral bone in rat models of knee
osteoarthritis treated by elcatonin

doi:10.3969/j.issn.2095-4344.2433

Abstract

Abstract:

BACKGROUND: Imbalance between subchondral bone resorption and bone formation occurs in osteoarthritis. Our preliminary study has found that the subchondral bone changes precede the articular cartilage changes in knee osteoarthritis rats.

OBJECTIVE: To observe the changes of subchondral bone in knee osteoarthritis rats, and to explore the effect of elcatonin on the expression of p38 MAPK and absorption of subchondral bone.

METHODS: Female Sprague-Dawley rats, 3 months of age, were randomly divided into three groups: sham operation group (n=6, the adipose tissue of the same size as the ovary was removed without ovariectomy, the bilateral knee joints were opened, but without cruciate ligament injury); model group (n=6, bilateral ovariectomy plus bilateral cruciate ligament injury, no treatment); elcatonin group (n=6, ovariectomy plus cruciate ligament injury, intramuscular injection of 5 IU/kg elcatonin, twice weekly). The bone mineral density and p38 protein expression levels in subchondral bone were detected at 12 weeks. The serum levels of C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen, interleukin-1, interleukin- 6 and bone-specific alkaline phosphatase, tartrate resistant acid phosphatase 5b were detected.

RESULTS AND CONCLUSION: (1) The bone volume fraction and trabecular bone number in the elcatonin group were significantly higher than those in the model group (P < 0.05), and the trabecular separation in the elcatonin group was lower than that in the model group (P < 0.05). (2) The bone volume fraction, trabecular bone number and trabecular thickness in the model group were lower than those in the sham operation group (P < 0.01 or P < 0.05), and the trabecular separation was higher than that in the sham operation group (P < 0.01). (3) The serum levels of C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen, interleukin-1, interleukin- 6 and tartrate resistant acid phosphatase 5b in the elcatonin group was significantly lower than those the model group (P < 0.05)，and the above levels in the model group were significantly higher than those in the sham operation group (P < 0.05). (4) The p38 expression level in subchondral bone in the elcatonin group was significantly lower than that in the model group (P < 0.01), and the level in the model group was significantly higher than that in the sham operation group (P < 0.01). (5) These results indicate that elcatonin may inhibit the secretion of osteoarthritis pro-inflammatory factors and subchondral bone resorption by down-regulating the expression level of p38 MAPK.

Key words: osteoarthritis, elcatonin, subchondral bone, bone resorption, p38 MAPK, bone tissue quantification, pro-inflammatory factor, tartrate resistant acid phosphatase 5b, bone-specific alkaline phosphatase, C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen

CLC Number:

Wu Qi, Liao Ying, Sun Guanghua, Zhou Guijuan, Liao Yuan, Liu Jing, Zhong Peirui, Cheng Guo, Deng Chengyuan, Wang Tiantian. Changes of subchondral bone in rat models of knee osteoarthritis treated by elcatonin[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(5): 709-715.

Figures/Tables 6

References

[1] PEREIRA D, RAMOS E, BRANCO J.Osteoarthritis.Acta Med Port.2015;28(1):99-106.
[2] LI G, YIN J, GAO J, et al.Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes.Arthritis Res Ther.2013;15(6):223.
[3] MORITA Y, ITO H, ISHIKAWA M, et al.Subchondral bone fragility with meniscal tear accelerates and parathyroid hormone decelerates articular cartilage degeneration in rat osteoarthritis model.J Orthop Res.2018;36(7):1959-1968.
[4] SCOTECE M, CONDE J, ABELLA V, et al.Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways.Cell Physiol Biochem. 2018;49(6):2414-2426.
[5] HU N, GAO Y, JAYASURIYA CT, et al. Chondrogenic induction of human osteoarthritic cartilage-derived mesenchymal stem cells activates mineralization and hypertrophic and osteogenic gene expression through a mechanomiR.Arthritis Res Ther.2019;21(1):167.
[6] HALL AC.The Role of Chondrocyte Morphology and Volume in Controlling Phenotype-Implications for Osteoarthritis, Cartilage Repair, and Cartilage Engineering.Curr Rheumatol Rep.2019;21(8):38.
[7] SEIDL CI, MURPHY CL.Dual and Opposing Regulation of MMP1 and MMP13 by Both Arms of miR-675 in Human Articular Chondrocytes.Cell Physiol Biochem. 2019;53(1): 172-185.
[8] MURAOKA T, HAGINO H, OKANO T, et al.Role of subchondral bone in osteoarthritis development: a comparative study of two strains of guinea pigs with and without spontaneously occurring osteoarthritis.Arthritis Rheum. 2007;56(10):3366-3374.
[9] VAN SPIL WE, KUBASSOVA O, BOESEN M, et al. Osteoarthritis phenotypes and novel therapeutic targets. Biochem Pharmacol. 2019;165:41-48.
[10] 钟培瑞,廖瑛,廖源,等.去卵巢对大鼠膝关节软骨及软骨下骨的影响[J].风湿病与关节炎,2017,6(11):5-10,20.
[11] AHO OM, FINNILÄ M, THEVENOT J, et al. Subchondral bone histology and grading in osteoarthritis. PLoS One.2017;12(3): e0173726.
[12] IZAWA T, HUTAMI IR, TANAKA E.Potential Role of Rebamipide in Osteoclast Differentiation and Mandibular Condylar Cartilage Homeostasis.Curr Rheumatol Rev.2018; 14(1):62-69.
[13] JUNG YK, HAN MS, PARK HR, et al.Calcium-phosphate complex increased during subchondral bone remodeling affects earlystage osteoarthritis.Sci Rep.2018;8(1):487.
[14] ZHOU Y, MING J, LI Y, et al.Ligustilide attenuates nitric oxide-induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways.J Cell Mol Med. 2019;23(5):3357-3368.
[15] LI WM, HAN CL, LIU C, et al.ANGPTL2 deletion inhibits osteoclast generation by modulating NF-κB/MAPKs/Cyclin pathways.Biochem Biophys Res Commun. 2018;503(3): 1471-1477.
[16] TSUKAMOTO M, MENUKI K, MURAI T, et al. Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells.Bone. 2016;85:70-80.
[17] BLANEY DEN, VAN CAAM AP, VAN DER KRAAN PM. Osteoarthritis year in review 2016: biology. Osteoarthritis Cartilage.2017;25(2):175-180.
[18] CHENG T, ZHANG L, FU X, et al.The potential protective effects of calcitonin involved in coordinating chondrocyte response, extracellular matrix, and subchondral trabecular bone in experimental osteoarthritis.Connect Tissue Res. 2013; 54(2):139-146.
[19] KETOLA JH, KARHULA SS, FINNILÄ MAJ, et al. Iterative and discrete reconstruction in the evaluation of the rabbit model of osteoarthritis.Sci Rep.2018;8(1):12051.
[20] HØEGH-ANDERSEN P, TANKÓ LB, ANDERSEN TL, et al. Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application.Arthritis Res Ther. 2004;6(2):R169-180.
[21] KAMEKURA S, HOSHI K, SHIMOAKA T, et al. Osteoarthritis development in novel experimental mouse models induced by knee joint instability.Osteoarthritis Cartilage.2005;13(7): 632-641.
[22] KATAE Y, TANAKA S, SAKAI A, et al.Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill-hole injuries in mice.J Orthop Res. 2009;27(12):1652-1658.
[23] WALLACH S, ROUSSEAU G, MARTIN L, et al.Effects of calcitonin on animal and in vitro models of skeletal metabolism.Bone.1999;25(5):509-516.
[24] MIMPEN JY, SNELLING SJB.Chondroprotective Factors in Osteoarthritis: a Joint Affair.Curr Rheumatol Rep. 2019;21(8): 41.
[25] LI X, HE P, HOU Y, et al.Berberine inhibits the interleukin-1 beta-induced inflammatory response via MAPK downregulation in rat articular chondrocytes.Drug Dev Res. Drug Dev Res. 2019 Apr 29.
[26] WANG CJ, CHENG JH, CHOU WY, et al.Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee.Int J Med Sci. 2017;14(3):213-223.
[27] CHEN K, LV ZT, ZHOU CH, et al.Peimine suppresses interleukin‑1β‑induced inflammation via MAPK downregulation in chondrocytes.Int J Mol Med.2019;43(5): 2241-2251.
[28] PARK C, JEONG JW, LEE DS, et al.Sargassum serratifolium Extract Attenuates Interleukin-1β-Induced Oxidative Stress and Inflammatory Response in Chondrocytes by Suppressing the Activation of NF-κB,p38 MAPK,and PI3K/Akt.Int J Mol Sci.Int J Mol Sci. 2018;19(8). pii: E2308.
[29] ZHANG R, WANG CM, JIANG HJ, et al.Protective Effects of Sweroside on IL-1β-Induced Inflammation in Rat Articular Chondrocytes Through Suppression of NF-κB and mTORC1 Signaling Pathway.Inflammation. 2019;42(2):496-505.
[30] ELLIOTT SF, COON CI, HAYS E, et al.Bcl-3 is an interleukin-1-responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene. Arthritis Rheum. 2002;46(12): 3230-3239.
[31] VINCENT TL.IL-1 in osteoarthritis: time for a critical review of the literature.F1000Res. F1000Res. 2019;8. pii: F1000 Faculty Rev-934.
[32] HAN PF, WEI L, DUAN ZQ, et al.Contribution of IL-1β, 6 and TNF-α to the form of post-traumatic osteoarthritis induced by "idealized" anterior cruciate ligament reconstruction in a porcine model.Int Immunopharmacol.2018;65:212-220.
[33] CHE ATNA, LAU SF, MOHAMED S.Ficus deltoidea Prevented Bone Loss in Preclinical Osteoporosis/ Osteoarthritis Model by Suppressing Inflammation.Calcif Tissue Int. 2018;103(4):388-399.
[34] CHEN X, CHEN X, ZHOU Z, et al.Nirogacestat suppresses RANKL-Induced osteoclast formation in vitro and attenuates LPS-Induced bone resorption in vivo.Exp Cell Res. 2019;15: 111470.
[35] OK SM, LEE SM, PARK HR, et al.Concentrations of CTX I, CTX II, DPD, and PYD in the urine as a biomarker for the diagnosis of temporomandibular joint osteoarthritis: A preliminary study. Cranio. 2018;36(6):366-372.
[36] SHEN J, ABU-AMER Y, O'KEEFE RJ, et al.Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res. 2017;58(1):49-63.
[37] ISHIDA M, KITAURA H, KIMURA K, et al.Muramyl dipeptide enhances lipopolysaccharide-induced osteoclast formation and bone resorption through increased RANKL expression in stromal cells.J Immunol Res.2015;2015:132765.
[38] ZHENG X, NIE Y, SUN C, et al.Long-term electroacupuncture stimulation prevents osteoporosis in ovariectomised osteopaenic rats through multiple signalling pathways. Acupunct Med. 2018;36(3):176-182.
[39] KARSDAL MA, HENRIKSEN K, ARNOLD M, et al. Calcitonin: a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality. BioDrugs.2008;22(3):137-144.
[40] SHIBAKAWA A, YUDOH K, MASUKO-HONGO K, et al.The role of subchondral bone resorption pits in osteoarthritis: MMP production by cells derived from bone marrow. Osteoarthritis Cartilage. 2005;13(8):679-687.
[41] ZHANG LB, MAN ZT, LI W, et al.Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-κB pathways. Mol Immunol.2017;87:249-257.
[42] VLOT MC, DEN HEIJER M, DE JONGH RT, et al.Clinical utility of bone markers in various diseases. Bone.2018;114: 215-225.
[43] GLENDENNING P, CHUBB SAP, VASIKARAN S.Clinical utility of bone turnover markers in the management of common metabolic bone diseases in adults.Clin Chim Acta. 2018;481:161-170.