Open Access

Serum levels of M-CSF, RANKL and OPG in rats fed with Kashin-Beck disease-affected diet

Journal of Orthopaedic Surgery and Research20149:78

https://doi.org/10.1186/s13018-014-0078-3

Received: 4 June 2014

Accepted: 8 August 2014

Published: 20 August 2014

Abstract

Objective

There were no studies on the macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in the pathogenesis of Kashin-Beck disease (KBD). The objective of the present study was to investigate the serum M-CSF, RANKL and OPG in rats fed with KBD-affected diet.

Methods

Ninety Wistar rats were divided into five groups. The rats received standard commercial feed with or without T-2 toxin additive, low protein feed with or without or T-2 toxin additive and the KBD-affected feed. The serum bioactivity of M-CSF, RANKL and OPG was tested by enzyme-linked immunosorbent assay.

Results

The serum levels of M-CSF in E group rats were higher than those in the other groups in the five groups (P < 0.01). The serum levels of RANKL and OPG in E group rats were highest in the five groups and have significant difference compared to the other groups (P < 0.05).

Conclusions

The molecule of M-CSF, RANKL and OPG may be involved in the regulation of epiphyseal plate injury and repair in KBD, and its participation in the pathogenesis of KBD should be studied in the future.

Keywords

Kashin-Beck disease Macrophage colony-stimulating factor Osteoprotegerin ligand receptor activator of NF-kappaB ligand Osteoprotegerin

Introduction

The important function of bone can be easily recognized in day-to-day life, where millions of people suffer from bone disease such as osteoporosis, which is, in part, caused by an imbalance between bone formation and bone resorption [1],[2]. The better understanding of the regulation of bone formation will provide new insights into the molecular mechanisms of Kashin-Beck disease (KBD), which usually afflicts children between the ages of 5 and 13 years with epiphyseal plates showing focal or irregular premature closure, wherein in the normal bone formation, endochondral ossification ends up about 20 years after birth in humans [3]-[5]. Its initial pathologic changes are multiple degenerative and necrotic lesions within the growth plate cartilage. The secondary pathologic findings, visible on radiographs, are repairing and remodeling around the necrotic foci of the cartilage of the metaphysis, bone end and epiphysis [6]-[9]. With the development of modern molecular biology technology, there has been a focus on serum biomarkers as tools in evaluating cartilage destruction [10]. However, there is little understanding of the expression of these biological molecules and the relationship with possible pathogenic factors of KBD.

Based on epidemiological investigations, three main hypotheses for the etiology of KBD are considered to be selenium deficiency in food, hypoalimenation in food and severe contamination of food by fungal mycotoxins [11]-[15]. The high altitude of the A'ba Autonomous Region of Sichuan province, just as Tibet, and the extremely severe weather conditions affect the availability of natural resources and the use of land. Due to high moisture content, the grains were particularly susceptible to mould and infected by fungi [16]-[18]. Cereal grain contamination by Fusarium spp. and Alternaria sp. in endemic areas of China, and cereal samples in high incidence areas of KBD were reported to be more heavily contaminated with trichotecenes (T-2 toxins) when compared to those in low incidence areas [19],[20]. Moreover, T-2 toxin can bind to the eukaryotic 60 S ribosomal subunit causing inhibition of protein, DNA and RNA synthesis. Although T-2 toxin can inhibit the proliferation of cartilage cells and reduce synthesis of proteoglycan and collagen in epiphyseal plate through metaphyseal rich and open capillary network, the fact is that the blood system was the first target of T-2 toxin involvement and bone marrow may be the main network place other than the epiphyseal plate. However, there has been little knowledge about the blood system and bone marrow biological process that have been regulated by T-2 toxin and the relationship with possible pathogenic factors of KBD.

It is generally believed that bone marrow contains progenitor cells both of osteoblasts and osteoclasts [21],[22]. On the basis of bone marrow biological process regulated by T-2 toxin, the microenvironment for progenitor cells in bone marrow may play an important role in the pathological changes of KBD [23]. At the molecular level, several factors are known to cooperate in regulating the sequential steps of endochondral bone formation in bone marrow, including the macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) [24]-[26]. RANKL is a transmembrane ligand expressed in osteoblasts and bone marrow stromal cells and produced by T cells. Following binding to RANK, a receptor vital for osteoclast differentiation, activation and survival, RANKL induces osteoclastogenesis in a pathway which synergizes with signals derived from M-CSF. OPG, also produced by osteoblasts and marrow stromal cells, lacks a transmembrane domain and acts as a decoy receptor for RANKL, thus regulating bone metabolism [27]. In view of the bone formation and KBD which usually afflicts children between the ages of 5 and 13 years with epiphyseal plates with focal or irregular premature closure, M-CSF/RANKL/OPG roles may be involved in the regulation of epiphyseal plate injury and repair in KBD. However, no paper has been published in this respect. In this study, the serum concentrations of M-CSF, RANKL and OPG were tested in order to evaluate their participation in the pathogenesis of KBD.

Materials and methods

Ninety weanling Wister rats (half were males and females, 4 weeks of age and with weight of 60 to 70 g) were obtained from the Center of Laboratory Animals of West China hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. The rats' rooms were maintained at a temperature of 22°C with relative humidity of 40%–70% and 12-h light/dark cycle. Prior to initiation of dosing, all rats were quarantined for 1 week and evaluated for weight gain and any gross sign of disease or injury. After quarantine, the rats were randomly divided by a computerized blocking procedure into five groups (every group has 18 rats). Group A was fed with a normal diet as control, group B was fed with a normal diet and T-2 toxin, group C was fed with a low nutrition diet and T-2 toxin, group D was fed with a low nutrition diet and group E was fed with a KBD-affected diet. All rats were supplied with tap water that is freely accessible at all times. Use of animals in this study was in accordance with NIH publication 85-23 ‘Guide for Care and Use of Laboratory Animals’ (NRC, 1996). The experiment was approved by the Animal Ethics Committee, West China school of Medicine, Sichuan University.

KBD-affected diet was made on the basis of the KBD-affected family dietary pattern by the wheat and corn samples, which were collected in October 2008 from KBD-affected family which was located in Jinchuan county of the A'ba region, Sichuan, People's Republic of China. Normal diet was based from the commercial rats' diet. The details of the dietary pattern and nutritional constitution of diet can be seen in our previous report [28],[29]. Every rat has been feed sufficiently to avoid conflict caused by hunger (20 to 30 g diet for each rat everyday). T-2 toxin was purchased from Trilogy Analytical Laboratory (Washington, MO, USA) at a purity of 99%; crystalline T-2 toxin was dissolved in absolute ethanol and diluted with 0.9% normal saline. The T-2 toxin was continuously administered intragastrically over 5 days in 1 week at levels of 0.04 mg/kg/day.

At 4, 8, and 12 weeks, six rats from each group were randomly sacrificed after collecting blood samples. After collection, blood samples were centrifuged and the serum obtained was stored at −80°C up to measurement. Serological investigations were carried out at the end of the study in all serum samples taken at the different time points. Assay were carried out to determine serum levels of M-CSF, RANKL and OPG by a sandwich enzyme-linked immunosorbent assay (ELISA), utilizing two monoclonal antibodies directed against separate antigenic determinants on the rat M-CSF, RANKL and OPG. The kits for the assay were provided by Adlitteram Diagnostic Laboratories Inc. (San Diego, CA, USA).

Statistical analyses

Statistical analyses were performed using SPSS Version 16.0 software. The data were expressed as the mean ± SD and were analyzed using analysis of variance (ANOVA). In the case of heterogeneity of variance, transformations were used to stabilize the variance. Results were considered statistically significant if the p value was less than 0.05 for continuous variables.

Results

ELISA analyses were used to determine the serum levels of M-CSF, RANKL and OPG in experiment rats (Table 1). The serum levels of M-CSF were similar in the control group and low nutrition group rats in the experience course at three time points (P > 0.05). The serum levels of M-CSF in E group rats were highest in the five groups at 4 and 8 weeks (411.85 ± 123.73 pg/ml versus 589.62 ± 147.85 pg/ml, respectively) and have significant difference compared to the other groups (P < 0.01). However, there were no differences in every group at 12 weeks (P > 0.05). C group rats just as the E group have the highest serum levels of M-CSF at 8 weeks and have significant difference compared to those at 4 weeks (376.30 ± 128.19 pg/ml versus 151.27 ± 81.22 pg/ml, P < 0.01).
Table 1

Serum levels of M-CSF, RANKL and OPG

Item

Time (weeks)

A

B

C

D

E

MCSF (pg/ml)

4

234.08 ± 82.08

116.61 ± 92.67

151.27 ± 81.22

246.76 ± 97.41

411.85 ± 123.73

 

8

231.36 ± 85.53*

138.82 ± 95.76*

376.30 ± 128.19*

259.64 ± 88.97*

589.62 ± 147.85**

 

12

232.56 ± 88.13

228.27 ± 76.63

250.77 ± 95.40

248.09 ± 93.52

258.87 ± 89.86

RANKL (ng/ml)

4

0.034 ± 0.025#

0.079 ± 0.038#

0.138 ± 0.059#

0.068 ± 0.017#

0.228 ± 0.085##

 

8

0.041 ± 0.017

0.084 ± 0.041

0.178 ± 0.022

0.052 ± 0.028

0.160 ± 0.059

 

12

0.058 ± 0.013

0.072 ± 0.038

0.153 ± 0.027

0.053 ± 0.011

0.105 ± 0.042

OPG (ng/ml)

4

1.415 ± 0.312※

1.492 ± 0.391※

1.734 ± 0.778※

1.324 ± 0.773※

2.688 ± 0.615※※

 

8

1.665 ± 0.597

1.542 ± 0.363

1.376 ± 0.369

1.486 ± 0.598

1.359 ± 0.517

 

12

1.672 ± 0.476

1.403 ± 0.624

1.241 ± 0.134

1.461 ± 0.708

1.288 ± 0.612

There were difference in the groups of * compared to **, # compared to ## and ※ compared to ※※, P < 0.01.

Mean ± SD.

The serum levels of RANKL in E group rats were highest at 4 weeks (0.228 ± 0.085 ng/ml), which have significant difference compared to the other groups at 4 weeks and compared to 8 or 12 week levels in E group (P < 0.01). At 8 and 12 weeks, C group rats have the highest serum levels of RANKL in five groups (0.178 ± 0.022 ng/ml versus 0.153 ± 0.027 ng/ml), which have significant difference compared to A, B and D (P < 0.05) and no significant difference compared to E (P > 0.05).

The serum levels of OPG were 2.688 ± 0.615 ng/ml in E group at 4 weeks, which was highest in the five groups and have significant difference compared to the other groups (P < 0.05). However, there were no significant differences among other groups at 4 weeks (P > 0.05). The serum levels of OPG were highest in the A group at 8 and 12 week time points (P > 0.05). At 8 and 12 weeks, the serum levels of OPG were 1.665 ± 0.597 ng/ml and 1.672 ± 0.476 ng/ml in A group rats, and there were no significant difference with the other groups (P > 0.05).

Discussion

Although the pathology of Kashin-Beck disease may be explained by the effect of mycotoxins, and different species of fungi produce a wide range of mycotoxins, low nutrition diet may be involved in the aetiology of KBD [10],[28]-[30].The A'ba region of Sichuan Province is an endemic area of KBD. It is located on the Tibetan plateau, which has a high altitude and high humidity and a low temperature region. The rat fed with KBD-affected diet shows focal necrosis and irregular premature closure at epiphysis plate by microscopy examination. The pathology of tibia growth cartilage and adjoining metaphyseal bone showed T-2 toxin combined with low nutrition diet which retarded the growth of rats similar to the changes of epiphysis plate with deep necrosis in KBD, and the necrotic lesions in epiphysis cartilage were multiple and localized in the deep zone of epiphyseal plate. The basic pathological change of KBD is the epiphyseal plate showing focal or irregular premature closure, which means that the normal bone formation of endochondral ossification was destroyed. However, the precise mechanism of chondrocyte necrosis and epiphyseal plate destruction in KBD remains unknown [31],[32].

KBD-affected diets and low nutrition diet, which was made on the basis of the KBD-affected family dietary pattern which lacks some of the nutritional elements, will lead to cell division, proliferation and self-repair capacity decline [28],[33]. Based on epidemiological investigations, mycotoxins are significantly associated with the risk of KBD [10]. Cereal samples in high incidence areas of KBD were found to be more seriously contaminated with trichothecenes when compared to those in low incidence areas [20]. Through the metaphyseal rich, open capillary network, T-2 toxin can inhibit the proliferation of cartilage cells and reduce synthesis of proteoglycan and collagen. Although T-2 toxin can induce the chondrocyte necrosis in animals, which bind to the eukaryotic 60 S ribosomal subunit causing inhibition of protein, DNA and RNA synthesis, it has no target cell specificity. Thus, the mycotoxin, which was seen as important environmental factors in the pathogenesis of Kashin-Beck disease, may have more complex network in the body, especially in the blood and bone marrow system [10]. The serum levels of M-CSF in KBD-affected diet group rats and low nutrition diet combined with T-2 toxin group rats were higher than those in the other groups, which means that the T-2 toxin not only induce the chondrocyte necrosis but also affect the metabolic process of M-CSF [34].

From the basic pathological change of epiphyseal plate showing focal or irregular premature closure in KBD, the destroyed bone formation of endochondral ossification that is investigated may be a key for a KBD study [30]. Recent studies have revealed an essential role of M-CSF and RANKL in the development of osteoclasts, and detailed molecular cascades that induce osteoclast differentiation, activation and apoptosis have been clarified [25]. Molecular mechanisms of RANK/RANKL/OPG are keys in osteoclast differentiation and activation in physiological and pathological conditions. When RANKL and M-CSF bind their receptors RANK and c-fms, respectively, osteoclast precursor cells differentiate into osteoclasts [27],[35],[36]. KBD-affected diets and low nutrition diet, which was made on the basis of the KBD-affected family dietary pattern that lacks some of nutritional elements, will lead to cell division, proliferation and self-repair capacity decline. The serum levels of RANKL were highest in the KBD-affected diet group rats.

The suppressed immunity and chronic hypoxia-induced mitochondrial damage and apoptosis may play an important role in the pathogenesis of KBD [37]-[39]. OPG interferes with the interactions between RANK and RANKL and inhibits osteoclast formation and function. It has been shown that the RANKL/OPG ratio may determine the delicate balance between bone resorption and synthesis [27]. Under normal conditions, RANKL is mainly produced by osteoblasts and bone marrow stromal cells. However, in many pathological conditions such as rheumatoid arthritis (RA) and neoplastic osteolysis, RANKL is also produced by T and B lymphocytes, macrophages/monocytes, fibroblasts, synoviocytes and megakaryocytes. T-2 toxin and its accumulating effect may cause a decrease in the normal rate of osteoprogenitor cell differentiation to osteoblasts and osteocytes [40]. The serum levels of OPG were highest in the KBD-affected group rats. Based on these previous studies [3]-[9], the aetiology of KBD not only causes epiphyseal plate chondrocyte necrosis but also decreases epiphyseal plate bone formation both by decreasing the rate of bone formation and increasing the bone resorption. Thus, the mycotoxin, which are seen as exogenous free-radical carriers, are important environmental factors in the pathogenesis of Kashin-Beck disease [41],[42], and selenium, vitamin C and vitamin E, which inhibit free-radical formation, are considered to be protective [12],[33].

Conclusion

The molecule of M-CSF, RANKL and OPG may be involved in the regulation of epiphyseal plate injury and repair in KBD, and its participation in the pathogenesis of KBD should be studied in the future.

Declarations

Acknowledgement

This research was funded by Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period (2007BA125B04) and National Natural Science Foundation of China (81271937).

Authors’ Affiliations

(1)
Nanshan Hospital of Shenzhen University
(2)
West China Hospital, Sichuan University
(3)
Third Hospital of Nanfang Medical University

References

  1. Berry PA, Maciewicz RA, Cicuttini FM, Jones MD, Hellawell CJ, Wluka AE: Markers of bone formation and resorption identify subgroups of patients with clinical knee osteoarthritis who have reduced rates of cartilage loss. J Rheumatol. 2010, 37: 1252-1259. 10.3899/jrheum.091055.View ArticlePubMedGoogle Scholar
  2. Sugata Y, Sotome S, Yuasa M, Hirano M, Shinomiya K, Okawa A: Effects of the systemic administration of alendronate on bone formation in a porous hydroxyapatite/collagen composite and resorption by osteoclasts in a bone defect model in rabbits. J Bone Joint Surg Br. 2011, 93: 510-516. 10.1302/0301-620X.93B4.25239.View ArticlePubMedGoogle Scholar
  3. Nesterov AI: The clinical course of Kashin-Beck disease. Arthritis Rheum. 1964, 7: 29-40. 10.1002/art.1780070105.View ArticlePubMedGoogle Scholar
  4. Sokoloff L: Kashin-Beck disease. Rheum Dis Clin North Am. 1987, 13: 101-104.PubMedGoogle Scholar
  5. Allander E: Kashin-Beck disease: an analysis of research and public health activities based on a bibliography 1849-1992. Scand J Rheumatol Suppl. 1994, 99: 1-36. 10.3109/03009749409117126.View ArticlePubMedGoogle Scholar
  6. Hinsenkamp M: Kashin-Beck disease. Int Orthop. 2001, 25: 133-10.1007/s002640000177.PubMed CentralView ArticlePubMedGoogle Scholar
  7. Hinsenkamp M, Ryppens F, Begaux F, Mathieu F, De Maertelaer V, Lepeire M, Haubruge E, Chasseur C, Stallenberg B: The anatomical distribution of radiological abnormalities in Kashin-Beck disease in Tibet. Int Orthop. 2001, 25: 142-146. 10.1007/s002640100236.PubMed CentralView ArticlePubMedGoogle Scholar
  8. Xiong G: Diagnostic, clinical and radiological characteristics of Kashin-Beck disease in Shaanxi Province, PR China. Int Orthop. 2001, 25: 147-150. 10.1007/s002640100248.PubMed CentralView ArticlePubMedGoogle Scholar
  9. Luo R, Liu G, Liu W, Pei F, Zhou Z, Li J, Shen B, Kang P, Xie Q, Ma X: Efficacy of celecoxib, meloxicam and paracetamol in elderly Kashin-Beck disease (KBD) patients. Int Orthop. 2011, 35: 1409-1414. 10.1007/s00264-010-1062-0.PubMed CentralView ArticlePubMedGoogle Scholar
  10. Yan D, Kang P, Shen B, Yang J, Zhou Z, Duan L, Pei F: Serum levels of IL-1beta, IL-6 and TNF-alpha in rats fed with Kashin-Beck disease-affected diet. Int J Rheum Dis. 2010, 13: 406-411. 10.1111/j.1756-185X.2010.01550.x.View ArticlePubMedGoogle Scholar
  11. Zhang WH, Neve J, Xu JP, Vanderpas J, Wang ZL: Selenium, iodine and fungal contamination in Yulin District (People's Republic of China) endemic for Kashin-Beck disease. Int Orthop. 2001, 25: 188-190. 10.1007/s002640100242.PubMed CentralView ArticlePubMedGoogle Scholar
  12. Peng A, Yang C, Rui H, Li H: Study on the pathogenic factors of Kashin-Beck disease. J Toxicol Environ Health. 1992, 35: 79-90. 10.1080/15287399209531597.View ArticlePubMedGoogle Scholar
  13. Chasseur C, Suetens C, Nolard N, Begaux F, Haubruge E: Fungal contamination in barley and Kashin-Beck disease in Tibet. Lancet. 1997, 350: 1074-10.1016/S0140-6736(05)70453-0.View ArticlePubMedGoogle Scholar
  14. Utiger RD: Kashin-Beck disease–expanding the spectrum of iodine-deficiency disorders. N Engl J Med. 1998, 339: 1156-1158. 10.1056/NEJM199810153391611.View ArticlePubMedGoogle Scholar
  15. Yao YF, Pei FX, Li XB, Yang J, Shen B, Zhou ZK, Li L, Kang PD: Preventive effects of supplemental selenium and selenium plus iodine on bone and cartilage development in rats fed with diet from Kashin-Beck disease endemic area. Biol Trace Elem Res. 2011, 146 (2): 199-206. 10.1007/s12011-011-9232-5.View ArticlePubMedGoogle Scholar
  16. Hinsenkamp M, Mathieu F, Claus W, Collard JF, de Maertelaer V, Gillet P, Nolard N, Lognay G: Effects of physical environment on the evolution of Kashin-Beck disease in Tibet. Int Orthop. 2009, 33: 1085-1088. 10.1007/s00264-009-0738-9.PubMed CentralView ArticlePubMedGoogle Scholar
  17. Suetens C, Moreno-Reyes R, Chasseur C, Mathieu F, Begaux F, Haubruge E, Durand MC, Neve J, Vanderpas J: Epidemiological support for a multifactorial aetiology of Kashin-Beck disease in Tibet. Int Orthop. 2001, 25: 180-187. 10.1007/s002640100247.PubMed CentralView ArticlePubMedGoogle Scholar
  18. Mathieu F, Begaux F, Lan ZY, Suetens C, Hinsenkamp M: Clinical manifestations of Kashin-Beck disease in Nyemo Valley, Tibet. Int Orthop. 1997, 21: 151-156. 10.1007/s002640050139.PubMed CentralView ArticlePubMedGoogle Scholar
  19. Haubruge E, Chasseur C, Debouck C, Begaux F, Suetens C, Mathieu F, Michel V, Gaspar C, Rooze M, Hinsenkamp M, Gillet P, Nolard N, Lognay G: The prevalence of mycotoxins in Kashin-Beck disease. Int Orthop. 2001, 25: 159-161. 10.1007/s002640100240.PubMed CentralView ArticlePubMedGoogle Scholar
  20. Chasseur C, Suetens C, Michel V, Mathieu F, Begaux F, Nolard N, Haubruge E: A 4-year study of the mycological aspects of Kashin-Beck disease in Tibet. Int Orthop. 2001, 25: 154-158. 10.1007/s002640000218.PubMed CentralView ArticlePubMedGoogle Scholar
  21. Kitamura H, Kawata H, Takahashi F, Higuchi Y, Furuichi T, Ohkawa H: Bone marrow neutrophilia and suppressed bone turnover in human interleukin-6 transgenic mice: a cellular relationship among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in bone marrow. Am J Pathol. 1995, 147: 1682-1692.PubMed CentralPubMedGoogle Scholar
  22. Bouvet-Gerbettaz S, Merigo E, Rocca JP, Carle GF, Rochet N: Effects of low-level laser therapy on proliferation and differentiation of murine bone marrow cells into osteoblasts and osteoclasts. Lasers Surg Med. 2009, 41: 291-297. 10.1002/lsm.20759.View ArticlePubMedGoogle Scholar
  23. Gwaltney SM, Galvin RJ, Register KB, Rimler RB, Ackermann MR: Effects of Pasteurella multocida toxin on porcine bone marrow cell differentiation into osteoclasts and osteoblasts. Vet Pathol. 1997, 34: 421-430. 10.1177/030098589703400506.View ArticlePubMedGoogle Scholar
  24. Ang ES, Pavlos NJ, Chim SM, Feng HT, Scaife RM, Steer JH, Zheng MH, Xu J: Paclitaxel inhibits osteoclast formation and bone resorption via influencing mitotic cell cycle arrest and RANKL-induced activation of NF-kappaB and ERK. J Cell Biochem. 2012, 113: 946-955. 10.1002/jcb.23423.View ArticlePubMedGoogle Scholar
  25. Fujita K, Janz S: Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG. RANKL and M-CSF. Mol Cancer. 2007, 6: 71-10.1186/1476-4598-6-71.PubMed CentralView ArticlePubMedGoogle Scholar
  26. Wilson SE, Mohan RR, Netto M, Perez V, Possin D, Huang J, Kwon R, Alekseev A, Rodriguez-Perez JP: RANK, RANKL, OPG, and M-CSF expression in stromal cells during corneal wound healing. Invest Ophthalmol Vis Sci. 2004, 45: 2201-2211. 10.1167/iovs.03-1162.View ArticlePubMedGoogle Scholar
  27. Karst M, Gorny G, Galvin RJ, Oursler MJ: Roles of stromal cell RANKL, OPG, and M-CSF expression in biphasic TGF-beta regulation of osteoclast differentiation. J Cell Physiol. 2004, 200: 99-106. 10.1002/jcp.20036.PubMed CentralView ArticlePubMedGoogle Scholar
  28. Yan D, Kang P, Yang J, Shen B, Zhou Z, Duan L, Deng J, Huang H, Pei FX: The effect of Kashin-Beck disease-affected feed and T-2 toxin on the bone development of Wistar rats. Int J Rheum Dis. 2010, 13: 266-272. 10.1111/j.1756-185X.2010.01530.x.View ArticlePubMedGoogle Scholar
  29. Yan D, Kang P, Li Y, Yang J, Shen B, Zhou Z, Deng J, Pei F: Radiographic findings of Wistar rats fed with T-2 toxin and Kashin-Beck disease-affected diet. Int J Rheum Dis. 2011, 14: 92-97. 10.1111/j.1756-185X.2010.01568.x.View ArticlePubMedGoogle Scholar
  30. Guo X, Zuo H, Cao CX, Zhang Y, Geng D, Zhang ZT, Zhang YG, von der Mark K, von der Mark H: Abnormal expression of Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage with Kashin-Beck disease. J Bone Miner Metab. 2006, 24: 319-328. 10.1007/s00774-006-0690-3.View ArticlePubMedGoogle Scholar
  31. Shokri F, Heidari M, Gharagozloo S, Ghazi-Khansari M: In vitro inhibitory effects of antioxidants on cytotoxicity of T-2 toxin. Toxicology. 2000, 146: 171-176. 10.1016/S0300-483X(00)00172-4.View ArticlePubMedGoogle Scholar
  32. Jaradat ZW, Viia B, Marquardt RR: Adverse effects of T-2 toxin on chicken lymphocytes blastogenesis and its protection with vitamin E. Toxicology. 2006, 225: 90-96. 10.1016/j.tox.2006.05.005.View ArticlePubMedGoogle Scholar
  33. Vanderpas J, Neve J: Kashin-Beck disease in China: osteochondrodysplasia related to nutrition and environment. Bull Mem Acad R Med Belg. 1999, 154: 177-184. discussion 184-179PubMedGoogle Scholar
  34. Hodge JM, Collier FM, Pavlos NJ, Kirkland MA, Nicholson GC: M-CSF potently augments RANKL-induced resorption activation in mature human osteoclasts. PLoS One. 2011, 6: e21462-10.1371/journal.pone.0021462.PubMed CentralView ArticlePubMedGoogle Scholar
  35. Zauli G, Rimondi E, Nicolin V, Melloni E, Celeghini C, Secchiero P: TNF-related apoptosis-inducing ligand (TRAIL) blocks osteoclastic differentiation induced by RANKL plus M-CSF. Blood. 2004, 104: 2044-2050. 10.1182/blood-2004-03-1196.View ArticlePubMedGoogle Scholar
  36. Itoh K, Udagawa N, Matsuzaki K, Takami M, Amano H, Shinki T, Ueno Y, Takahashi N, Suda T: Importance of membrane- or matrix-associated forms of M-CSF and RANKL/ODF in osteoclastogenesis supported by SaOS-4/3 cells expressing recombinant PTH/PTHrP receptors. J Bone Miner Res. 2000, 15: 1766-1775. 10.1359/jbmr.2000.15.9.1766.View ArticlePubMedGoogle Scholar
  37. Wang S, Guo X, Wu XM, Lammi MJ: Genome-wide gene expression analysis suggests an important role of suppressed immunity in pathogenesis of Kashin-Beck disease. PLoS One. 2012, 7: e28439-10.1371/journal.pone.0028439.PubMed CentralView ArticlePubMedGoogle Scholar
  38. Zhang F, Guo X, Wang W, Yan H, Li C: Genome-wide gene expression analysis suggests an important role of hypoxia in the pathogenesis of endemic osteochondropathy Kashin-Beck disease. PLoS One. 2011, 6: e22983-10.1371/journal.pone.0022983.PubMed CentralView ArticlePubMedGoogle Scholar
  39. Du Hong X, Xia Dai X, Xia Song R, Zhen Zou X, Yan Sun W, Yan Mo X, Lu Bai G, Min Xiong Y: SNP and mRNA expression for glutathione peroxidase 4 in Kashin-Beck disease. Br J Nutr. 2012, 107: 164-169. 10.1017/S0007114511002704.View ArticleGoogle Scholar
  40. Guan F, Li S, Wang ZL, Yang H, Xue S, Wang W, Song D, Zhou X, Zhou W, Chen JH, Caterson B, Hughes C: Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions. Rheumatol Int. 2013, 33 (1): 157-166. 10.1007/s00296-011-2335-7.View ArticlePubMedGoogle Scholar
  41. Vila B, Jaradat ZW, Marquardt RR, Frohlich AA: Effect of T-2 toxin on in vivo lipid peroxidation and vitamin E status in mice. Food Chem Toxicol. 2002, 40: 479-486. 10.1016/S0278-6915(01)00122-3.View ArticlePubMedGoogle Scholar
  42. Minervini F, Fornelli F, Lucivero G, Romano C, Visconti A: T-2 toxin immunotoxicity on human B and T lymphoid cell lines. Toxicology. 2005, 210: 81-91. 10.1016/j.tox.2005.01.007.View ArticlePubMedGoogle Scholar

Copyright

© Yan et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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.

Advertisement