Study On Correlation Between Clinic And The Expression Of Interleukin-1 And Interleukin-6 In The Osteophyma And The Tissue Cohering On It From The Medial Of The First Metatarsal Bone Head Of Hallux Valgus

1 BackgroundHallux valgus is a kind of complicate forefoot deformity disease, which is very common and frequently encountered disease in clinic. The main symptoms of it are lateral displacement of the great toe, producing deformity of the first metatarsophalangeal joint with callous, bursa, or bunion formation over the bony prominence and pain in forefoot. The incidence rate of hallux valgus has reached to 10-20% in our country. Among them 95% patients are women. There are almost ten million people especially middle-aged and old women who need to be treated every year. The research on hallux valgus is one hot spot of the subjects of foot-surgery home and aboard constantly.The pain situates in forefoot is the main reason which leads patients to visit doctors. There are many difference opinions on the reasons of pain of hallux valgus. The most popular opinion is the constant friction and pressurization between the medial of the first metatarsophalangeal join and shoes lead to bunion formation over the bony prominence and pain. The theory above has been used for many years. Nevertheless, we found the pain of the most hallux valgus patients though situates in the medial part of the first metatarsal head in clinic. The pain is not always in the same parts and the characters of pain are also difference. There are a lot of patients whose symptoms of pain lie in the extremital parts of musculus abductor hallucis and breviflexor hallucis not in skin and hypodermic tissue. The symptoms indicate that the extremital structures of these muscles have pathological changes. Recently my editor professor Wen Jian-min has undertaken a system study on the main symptoms and physical signs of hallux valgus, anatomy of forefoot and the medial tissue of the first metatarsophalangeal join. He supposed that the medial of the first metatarsophalangeal join is a kind of extremital structure. Enthesiopathy of abductor hallucis is one of the reasons that cause the pain of hallux valgus.The pain of hallux valgus reflects the disease of Tai-yin Jing-jin of foot when we use the theory of Jing-jin of Traditional Chinese Medicine (TCM) to analyze the symptoms and the disease course. We found Tai-yin Jing-jin of foot beginning from the medial of big toe, and then along the first ray of foot arrive at medial malleolus. The route of it just pass away medial of the first metatarsophalangeal joint. We also found spots of disease such as Da-du-ci and Gong-sun-ci along with the Tai-yin Jing-jin of foot which including the first metatarsal head, the first metatarsophalangeal joint, abductor hallucis and flexor hallucis brevis according to anatomy. Jin-jing and Jin-niu are the most frequent spots being injured. They are extremital structure according to anatomy of modern medicine. Extremital structure can be damaged by acute or chronic trauma, which leads to Enthesiopathy.The patients of hallux valgus usually have arthrocele, pain and activity limitation of the first metatarsophalangeal joint. The X-ray of foot can find the signs of osteoarthritis of the first metatarsophalangeal joint which have articular surface indurascent, accrementition of the edge of the joint, joint space stenosis et al. These symptoms, physical and X-ray signs appeared earlier and severer than the normal persons of the same age. The osteoarthritis of the first metatarsophalangeal joint is also one of the reasons of the pain of hallux valgus.The osteoarthritis of the first metatarsophalangeal joint is one of complications of hallux valgus. Osteoarthritis belongs to Bi-zheng or Gu-bi of Traditional Chinese Medicine (TCM). They are cause and effect each other. Following aging ZANG-organ of Gan and Shen keep decline day by day. The bones and muscles haven't enough nutrition to nourish themselves. And then pain and activity limitations of the joints appear, even following malformation of joints and disability.So there seemed improper to explain the pain of hallux valgus only using bunion. Many-sided factors result in the pain of hallux valgus. The pain doses not only lie in the skin and medial subcutaneous tissue of the first metatarsophalangeal joint that suffer friction and crushing. Osteoarthritis of the first metatarsophalangeal joint and enthesiopathy of abductor hallucis also cause pain. They have close correlation with the pain of hallux valgus.Following the development of modern genetics, molecular biology and genetic engineering, the study on aetiology has entered molecule and gene level. As the main inflammatory factors, firstly, Interleukin-1 and Interleukin-6 have deep correlation with the etiological factor and pathology of OA. Secondly, in the pain field,Interleukin-1 and Interleukin-6 can cause hyperalgia directly or indirectly, and intension of pain has positive correlation with the quantity of them. Perhaps IL-1 itself is a kind of strong algesic substance. IL-1 and IL-6 also can cause hyperalgia through increasing the expression of P substance, stimulating nocicepter to depolarize. Nowadays there are many studies of IL-1 and IL-6 on the etiological factor and pathology of OA and RA, yet the studies of IL-1 and IL-6 on the etiological factor and pathology of hallux valgus are still blank. Whether IL-1 and IL-6 have positive expression in the medical tissue of hallux valgus or not? What are the relationship between IL-1 and IL-6 positive expression and the first metatarsophalangeal joint and enthesiopathy of abductor hallucis? Whether there is a correlation between IL-1 and IL-6 and pain of hallux valgus or not? There are so many questions need to be studied deeply.2 PurposesThrough detecting the positive cells expression and mean optical density (MOD) of IL-1 and IL-6 in the osteophyma and the tissue on them (including part of articular cartilage, articular capsule, subcutaneous tissue and skin) of the first metatarsophalangeal joint of hallux valgus patients and combining the clinical manifestation to analyze and induce. Research the pathology changes of hallux valgus through molecular level. Explore the development mechanisms of the pathology changes of hallux valgus. Approach the correlation between the pathology changes and the clinical manifestation. Further the knowledge of hallux valgus disease. Provide scientific foundation for the diagnoses and treatments. And expend the new therapy methods of hallux valgus.3 Materials and methods 3.1 General materials(1) 56 cases of intact osteophyma and the tissue cohering on it (including part of articular cartilage, articular capsule, subcutaneous tissue and skin) from the medical part of the first metatarsal bone head which take out from 56 feet with hallux valgus by Minimal incision technique.(2) 6 fresh feet specimens as control grope the same methods are used to take out the intact tissue of the medical part of the first metatarsal bone head including part of articular cartilage, articular capsule, subcutaneous and skin tissue.(3) 56 cases (56 feet) were obtained from 113 cases which are the patients with hallux valgus in our department Wang-jing hospital from October 2004 to May 2005.1) the scores of pain which according to the patients' histories, symptoms and physical signs apply to 6-point behavioral rating scale (BRS-6), 2) the measurements of hallux abductus angle (HAV) X-ray of feet and 3) the gradings of OA of the first metatarsophalangeal joint according to Kellgren-Lawrence grading system.3.2 Operation methodHave an arc incision about lcm in the distal and medical part of the first metatarsophalangeal joint, and then cut off the skin and use a special drill cut off the osteophyma and the soft tissue cohering on it from the medical part of the metatarsal head. Another incision which length is about 0.5cm is done on the medical part of the neck of the first metatarsal bone, use the drill to cut off the basilar part of the osteophyma and then take out the osteophyma.3.3 Methods to deal with specimensThe specimens were fixed, decalcificated, dehydration, embedding and sliced step by step.3.4 Measurement and quantitative analysisThe positive cell expression of IL-1 and IL-6 was detected by immunohistochemical staining and quantitatively analyzed by computer image analysis system, positive cell number counted and mean optical density measured.3.5 Handling of the dataSPSS 12.0 statistical package was used. According different data use different correlation coefficient analysis.4 Results4.1 The correlation between HAV angle, KL degrees and pain gradingof BRS-6(1) The Spearman correlation coefficient (rs) between the HAV angles and the KL degrees of hallux valgus patients is 0.844, P<0.001. A significant correlation exists between them. (2)The rs between the HAV angles and pain grading of BRS-6 of hallux valgus patients is 0.200, P>0.05. No definite correlation exists between them. (3) The rs between the KL degrees and pain grading of BRS-6 of hallux valgus patients is0.146, P>0.05. No definite correlation exists between them.4.2 Positive cell expression of IL-1 and IL-6 results in both hallux valgus and control groupIn 56cases (56feet), positive cell expression of IL-1 is 53cases. The percentage is 94.6%. IL-6 is 52cases (92.9%). Both IL-1 and IL-6 is 50cases(89.3%). lease has not positive cell expression either IL-1 or IL-6. lease has a little positive cell expression on surface of arthrodial cartilage in control group (5feet). 1) IL-1 and IL-6 positive cell expression parts of hallux valgus medical tissue specimen mainly lie in arthrodial cartilage and juncture of tendon-bone (extremity structure). There is no significant difference between IL-1 and IL-6. 2) In the specimens the main positive cell are chondrocyte, osteocyte, desmocyte, lymphocyte and a little synoviocyte. There is no significant difference between IL-1 and IL-6.4.3 The results of positive cell counting and mean optical density in arthrodial cartilage and extremity structure.The positive cell numbers of IL-1 in arthrodial cartilage are P2.5 = 5.57, P975 — 53.05 and MOD=0.22+ 0.06OD. IL-6 are P2.5 = 7.09, P97.5 = 55.63 and MOD=0.21 ±0.05OD. The positive cell numbers of IL-1 in extremity structure are P2.5 = 6.46, P97.5 = 85.15 and MOD=0.21±0.06OD. IL-6 are P25=2.66, P97.5 = 70.10 and MOD =0.21±0.05OD.4.4 The correlation between HAV angle and positive cell counting and mean optical density of IL-land IL-6 in arthrodial cartilage and extremity structureThe rs of HAV angle and positive cell counting of IL-1 in arthrodial cartilage is 0.275, P<0.05 (2-tailed). IL-6 is 0.493, P<0.05 (2-tailed). A significant correlation exists between them. No definite correlation exists between MOD of IL-1 and IL-6 and HAV angle, P>0.05 (2-tailed) . Neither positive cell counting nor mean optical density of IL-1 and IL-6 in arthrodial cartilage have definite correlation with HAV angle, P>0.05 (2-tailed) . Neither positive cell counting nor mean optical density of IL-land IL-6 in extremity structure have definite correlation with HAV angle, P> 0.05 (2-tailed) .4.5 The correlation between the first metatarsophalangeal joint KL grades and positive cell counting and mean optical density of IL-land IL-6 in arthrodial cartilageThe rs of the first metatarsophalangeal joint KL grades and positive cell countingof IL-lis 0.316, P<0.05 (2-tailed) .IL-6 is 0.343, P<0.05 (2-tailed) . A significant correlation exists between them. No definite correlation between MOD of IL-1 and IL-6 and the first metatarsophalangeal joint KL grades, P>0.05 (2-tailed) . 4.6 The correlation between positive cell counting and mean optical density of IL-land IL-6 in arthrodial cartilage and extremity structure and the grades of BRS-6Neither positive cell counting nor mean optical density of IL-1 in arthrodial cartilage have definite correlation with the grades of BRS-6, P>0.05 (2-tailed) . The rs of positive cell counting of IL-6 and the grades of BRS-6 is 0.397, P<0.05 (2-tailed) . A significant correlation exists between them. No definite correlation exists between MOD of IL-6 in arthrodial cartilage and the grades of BRS-6. Neither positive cell counting nor mean optical density of IL-land IL-6 in extremity structure have definite correlation with the grades of BRS-6, P>0.05 (2-tailed) .5 Conclusions(l)The positive cell expression of IL-1 and IL-6 is significant in the medical tissue of hallux valgus. The main parts of expression lie on extremity structure and arthrodial cartilage, which indicates they are the main parts of pathological changes.(2) IL-1 and IL-6 positive expression in extremity structure and arthrodial cartilage indicate that Enthesiopathy of abductor hallucis and OA of the first metatarsophalangeal joint are the key internal factors which provoke pain of hallux valgus and lead to the deformity development of hallux valgus.(3) IL-1 and IL-6 are the cytokines which play important roles in the field of the etiopathogenisis and pathology in hallux valgus.