_膝關(guān)節(jié)原發(fā)性骨關(guān)節(jié)炎軟骨和軟骨下骨病理改變的定量研究_圖文

1、膝關(guān)節(jié)原發(fā)性骨關(guān)節(jié)炎軟骨和軟骨下骨病理改變的定量研究宋偉楊柳王富友【摘 要】目的 觀察膝關(guān)節(jié)原發(fā)性骨關(guān)節(jié)炎(osteoarthritis,OA脛骨平臺軟骨和軟骨下骨病理改變特點,對比內(nèi)、外側(cè)平臺軟骨和軟骨下骨結(jié)構(gòu)參數(shù),探討鈣化層和軟骨下骨在OA發(fā)病機制中的作用。方法取2009年10月-2011年5月行人工全膝關(guān)節(jié)置換術(shù)治療的30例30膝原發(fā)性O(shè)A患者自愿捐贈的新鮮脛骨平臺標(biāo)本進行實驗。其中男11例,女19例;年齡5578歲,平均65.1歲。病程1025年,平均16.6年;患膝內(nèi)翻畸形123,平均9.3。大體觀察脛骨平臺后在內(nèi)、外側(cè)中央負重區(qū)取材,常規(guī)制備脫鈣石蠟切片,行HE和番紅O/固綠染色,

2、觀察關(guān)節(jié)軟骨退變特點,參照Mankin評分標(biāo)準(zhǔn)評分并分期;觀察鈣化層及軟骨下骨病理改變。應(yīng)用Image Pro Plus 6.0圖像分析軟件測量軟骨和軟骨下骨結(jié)構(gòu)參數(shù),包括軟骨全層(total articular cartilage,TAC厚度、鈣化層(articular calci ed cartilage,ACC厚度、ACC/TAC比值、軟骨下骨板(subchondral bone plate,SCP厚度以及骨小梁體積分數(shù)(trabecular bone volume, BV/T V。結(jié)果大體觀察內(nèi)側(cè)平臺軟骨退變較外側(cè)嚴重,內(nèi)側(cè)平臺軟骨Mankin評分為(12.4 1.1分,顯著高于外側(cè)平

3、臺的(8.3 1.6分(t=12.173,P=0.000。根據(jù)Mankin評分結(jié)果在60個標(biāo)本中,14個為OA早期,可見軟骨淺表層裂隙、潮線復(fù)制和軟骨下骨增厚;19個為OA中期,可見軟骨深層裂隙、多發(fā)軟骨下骨吸收陷窩和明顯增厚的軟骨下骨;27個為OA晚期,可見軟骨全層缺失、軟骨內(nèi)化骨和“象牙化”軟骨下骨。軟骨和軟骨下骨結(jié)構(gòu)參數(shù)測定示:內(nèi)側(cè)平臺TAC厚度顯著低于外側(cè)平臺,ACC/TAC比值、BV/TV及SCP厚度顯著高于外側(cè)平臺,差異均有統(tǒng)計學(xué)意義(P 0.05。結(jié)論鈣化層和軟骨下骨可能在OA發(fā)生與進展中發(fā)揮了重要作用?！娟P(guān)鍵詞】原發(fā)性骨關(guān)節(jié)炎非鈣化軟骨鈣化層軟骨下骨圖像分析HISTOMORPH

4、OMETRIC ANALYSIS OF ARTICULAR CARTILAGE AND SUBCHONDRAL BONE FROM PRIMARY OSTEOARTHRITIC KNEES/SONG Wei, YANG Liu, WANG Fuyou. Center for Joint Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, P.R.China. Corresponding author: YANG Liu, E-mail: jointsurgery 【Abstract

5、】Objective To investigate the pathologic characteristics of the articular cartilage and subchondral bone from osteoarthritic knees, and to compare the structural parameters of articular cartilage and subchondral bone between the medial and lateral tibial plateau, so as to determine the role of calci

6、fied zone and subchondral bone in the pathogenesis of osteoarthritis (OA. Methods The tibial plateaus were taken from 30 patients undergoing total knee arthroplasty between October 2009 and May 2011. The subjects included 11 males and 19 females with an average age of 65.1 years (range, 55-78 years.

7、 The mean disease duration was 16.6 years (range, 10-25 years; the mean varus angle of the diseased knee was 9.3 (range, 1-23. After gross observation, the cartilage-bone samples were taken out from the most weight-bearing regions in the internal areas of the medial and lateral plateaus. The decalci

8、 ed paraf n-embedded sections were prepared and stained with HE and Safranin O/fast green for cartilage assessment (Mankin score, staging, and bone histomorphometry; the pathologic features of the cartilage and subchondral bone were also observed. The thickness of total articular cartilage (TAC, art

9、icular calci ed cartilage (ACC, subchondral bone plate (SCP, and the trabecular bone volume (BV/TV were measured by Image Pro Plus 6.0 imaging system, then the ratio of ACC/TAC was calculated. Results Macroscopic results showed that articular cartilage degeneration was more severe in the medial plat

10、eau than in the lateral plateau; Mankin score of the medial plateau (12.4 1.1 was signi cantly higher than that of the lateral plateau (8.3 1.6 (t=12.173, P=0.000. In the 60 samples, 14 samples were at stage I, characterisd by ssures within the super cial zone, duplicated tidemark, and thickend subc

11、hondral bone; 19 samples were at stage II, characterisd by ssures extending into the deep zone, multiple subchondral bone resorption pits, and obviously thickend subchondral bone; and 27 samples were at stage III, characterisd by full-thickness cartilage defects, endochondral ossification, and eburn

12、ated subchondral bone. The bone histomorphometric study showed that TAC thickness of the medial plateau was signi cantly lower than that of the lateral plateau (P 0.05; the ratios of ACC/TAC, BV/TV, and SCP thickness基金項目:國家自然科學(xué)基金面上項目(30870639;國家自然科學(xué)基金重點項目(31130021作者單位:第三軍醫(yī)大學(xué)西南醫(yī)院關(guān)節(jié)外科中心(重慶,400038通訊作者:

13、楊柳,教授,博士生導(dǎo)師,研究方向:組織工程和關(guān)節(jié)外科,E-mail: jointsurgery網(wǎng)絡(luò)出版時間:2011-11-12 21:15:14;網(wǎng)絡(luò)出版地址:of the medial plateau were signi cantly higher than those of the lateral plateau (P 0.05. Conclusion The calcified zone and subchondral bone may play an important role in the initiation and progression of OA.【Key words】

14、 Primary osteoarthritis Uncalcified articular cartilage Calcified zone Subchondral bone Imaging analysisFoundation items: National Natural Science Foudation of China(30870639; Key Program of National Natural Science Foundation of China (31130021膝關(guān)節(jié)原發(fā)性骨關(guān)節(jié)炎(osteoarthritis,OA是臨床上最常見的關(guān)節(jié)疾患之一,常合并內(nèi)翻畸形,以進行性

15、軟骨退變和軟骨下骨重塑為主要特點,是力學(xué)和生物學(xué)因素共同作用下軟骨細胞、細胞外基質(zhì)、軟骨下骨三者合成與分解失衡的結(jié)果。以往對OA的研究多集中在非鈣化軟骨,認為軟骨細胞凋亡、軟骨基質(zhì)降解是OA的主要發(fā)病機制1。然而,近年來許多研究表明OA的發(fā)生可能源于軟骨下骨和鈣化層結(jié)構(gòu)2-3。軟骨下骨包括軟骨下骨板和骨小梁,軟骨下骨和鈣化層又統(tǒng)稱為軟骨下礦化組織4。鈣化層、軟骨下骨板和骨小梁具有不同的形態(tài)結(jié)構(gòu)和機械力學(xué)性能,在OA中都發(fā)生了特異性改變,和軟骨退變密切相關(guān)。本實驗以膝關(guān)節(jié)OA標(biāo)本為研究對象,對比脛骨內(nèi)、外側(cè)平臺軟骨和軟骨下骨結(jié)構(gòu)參數(shù),為進一步研究OA的發(fā)病機制和預(yù)防、治療方法提供理論依據(jù)。1材料

16、與方法1.1 實驗標(biāo)本實驗用新鮮脛骨平臺標(biāo)本由2009年10月-2011年5月在第三軍醫(yī)大學(xué)西南醫(yī)院關(guān)節(jié)外科中心行人工全膝關(guān)節(jié)置換術(shù)治療的30例原發(fā)性O(shè)A患者自愿捐贈,均排除類風(fēng)濕性關(guān)節(jié)炎、創(chuàng)傷、感染、腫瘤等其他疾病。其中男11例11膝,女19例19膝;年齡5578歲,平均65.1歲;病程1025年,平均16.6年?；颊咝g(shù)前攝雙下肢負重位等比例X線片,測量下肢力線和患膝內(nèi)翻角度,內(nèi)翻畸形123,平均9.3。1.2主要試劑與儀器番紅O、固綠染色劑(Sigma公司,美國。CKX31顯微鏡及圖像采集系統(tǒng)(Olympus公司,日本;Image Pro Plus 6.0圖像分析軟件(Media Cybe

17、rnetics公司,美國。1.3 實驗方法1.3.1 大體觀察術(shù)中獲取新鮮脛骨平臺標(biāo)本后,觀察脛骨平臺軟骨外觀、顏色、光澤度,有無軟骨軟化、潰瘍、裂隙、血管翳樣組織和骨贅形成等。1.3.2 組織學(xué)觀察大體觀察后分別在脛骨平臺內(nèi)、外側(cè)中央負重區(qū)切取骨軟骨組織塊,共計60個標(biāo)本,大小為1.5 cm 1.0 cm 1.0 cm。置于10%甲醛溶液固定24 h,15%中性EDTA-2Na脫鈣15 d,經(jīng)梯度脫水、石蠟包埋后作厚5 m連續(xù)切片。切片分別行HE和番紅O/固綠染色,觀察軟骨、鈣化層和軟骨下骨病理改變情況。于番紅O/固綠染色切片參照Mankin評分標(biāo)準(zhǔn)5對軟骨退變程度進行評分;并根據(jù)Manki

18、n評分將OA病程分為3期6,期(早期,06分;期(中期,79分;期(晚期,1014分。1.3.3 軟骨及軟骨下骨結(jié)構(gòu)參數(shù)測定每個標(biāo)本取3張番紅O/固綠染色的不連續(xù)切片,每張切片隨機選取5個視野,于40倍光鏡下應(yīng)用Image Pro Plus 6.0圖像分析軟件,按照骨組織形態(tài)計量學(xué)方法7測量軟骨和軟骨下骨結(jié)構(gòu)參數(shù),測量結(jié)果取均值。5個結(jié)構(gòu)參數(shù)分別為:軟骨全層(total articular cartilage, TAC厚度:軟骨表層至黏合線之間的距離;鈣化層(articular calci ed cartilage,ACC厚度:末條潮線至黏合線之間的距離;軟骨下骨板(subchondral b

19、one plate,SCP厚度:黏合線至軟骨下骨板與骨小梁交界處之間的距離;骨小梁體積分數(shù)(trabecular bone volume,BV/T V:測量范圍內(nèi)骨小梁面積/(骨小梁+骨髓腔面積 100%;ACC/TAC比值:ACC/TAC 100%。1.4統(tǒng)計學(xué)方法采用SPSS13.0統(tǒng)計軟件包進行分析。計量資料以均數(shù)標(biāo)準(zhǔn)差表示,組間比較采用配對t檢驗;檢驗水準(zhǔn)=0.05。2 結(jié)果2.1 大體觀察所有標(biāo)本內(nèi)側(cè)平臺軟骨退變均較外側(cè)嚴重。內(nèi)側(cè)平臺軟骨表面粗糙、無光澤,呈灰黃色,可見廣泛軟化灶、巨大裂隙,多見軟骨下骨暴露、象牙化,見血管翳樣組織覆蓋,平臺中央和邊緣多發(fā)骨贅形成。外側(cè)平臺軟骨相對正常

20、,軟骨表面尚平整、局部有光澤,多見散在的淺表潰瘍、軟化灶,少見裂隙形成,無軟骨全層缺失,無血管翳樣組織形成,部分標(biāo)本可見邊緣骨贅。見圖1。2.2組織學(xué)觀察2.2.1 軟骨退變病理觀察和Mankin評分內(nèi)側(cè)平臺軟骨Mankin評分為(12.4 1.1分,顯著高于外側(cè)平臺的(8.3 1.6分,差異有統(tǒng)計學(xué)意義(t=12.173, P=0.000。根據(jù)Mankin評分結(jié)果在60個標(biāo)本中,14個為OA早期,番紅O/固綠染色見軟骨淺表層連續(xù)性中斷,水平或垂直裂隙形成局限于淺表層,伴有軟骨細胞凋亡。19個為OA中期,裂隙進入軟骨深層,裂隙周圍軟骨細胞增殖、簇集、基質(zhì)淡染。27個為OA晚期,軟骨全層缺失,軟

21、骨下骨暴露、象牙化,可伴有肉芽組織生成覆蓋裸露軟骨下骨或殘留透明軟骨。見圖2。2.2.2 鈣化層和軟骨下骨病理觀察在OA各期均可觀察到鈣化層重塑現(xiàn)象。OA早期:潮線復(fù)制、前移,兩條潮線之間可見簇集、肥大的軟骨細胞;鈣化層微裂隙形成,長度為30100 m,可向下延伸到軟骨下骨板。OA中期:多發(fā)軟骨下骨吸收陷窩,參照分級標(biāo)準(zhǔn)8分為3級,1個標(biāo)本為0級,無血管侵入;12個為1級,血管局限在鈣化層,未超過潮線;6個為2級,血管越過潮線進入非鈣化軟骨。OA晚期:多見軟骨內(nèi)化骨現(xiàn)象,鈣化層在侵入血管的作用下向骨組織轉(zhuǎn)化,鈣化層厚度減小,甚至完全缺失。見圖3 ae。在OA各期軟骨下骨同樣出現(xiàn)典型病理改變。O

22、A 早期:軟骨下骨板和骨小梁輕度增厚。OA中期:軟骨下骨板和骨小梁厚度明顯增加,局部軟骨下骨暴露伴肉芽組織覆蓋。OA晚期:廣泛軟骨下骨暴露、象牙化,骨小梁中可見軟骨下骨囊腫形成和軟骨樣組織沉積。見圖3 fi。2.3 軟骨和軟骨下骨結(jié)構(gòu)參數(shù)測定內(nèi)側(cè)平臺TAC厚度顯著低于外側(cè)平臺,ACC/TAC 比值、BV/TV及SCP厚度顯著高于外側(cè)平臺,差異均有統(tǒng)計學(xué)意義(P 0.05。見表1。3討論3.1機械力學(xué)因素在OA發(fā)病機制中的作用膝內(nèi)翻可加快內(nèi)側(cè)關(guān)節(jié)間隙狹窄9、內(nèi)側(cè)平臺軟骨丟失速度,而外翻畸形可延緩內(nèi)側(cè)平臺軟骨丟失速度10。實驗中選取標(biāo)本均為膝關(guān)節(jié)OA伴內(nèi)翻畸形者,內(nèi)側(cè)平臺Mankin評分顯著較外側(cè)

23、平臺增高,表明下肢力線改變所致應(yīng)力異常集中是OA發(fā)病的重要因素之一。脛骨高位截骨術(shù)(high tibial osteotomy,HTO可矯正下肢對線不良,卸載內(nèi)側(cè)脛股關(guān)節(jié)過度負荷,適用于年輕、活動量大、單純內(nèi)側(cè)間室OA患者。血管翳樣組織是一種特殊的肉芽組織,常常覆蓋殘留透明軟骨或裸露軟骨下骨,來源于BMSCs,主要由纖維軟骨細胞和少量纖維組織構(gòu)成,可合成、型膠原和蛋白聚糖,為一種外源性纖維軟骨修復(fù)機制11。HTO術(shù)后關(guān)節(jié)鏡檢查發(fā)現(xiàn)血管翳樣組織大量生成覆蓋負重區(qū)“象牙化”軟骨下骨,提示通過矯形術(shù)恢復(fù)正常生物力學(xué)環(huán)境有利于纖維軟骨細胞增殖12,調(diào)控血管翳樣組織中纖維軟骨細胞表型以合成正常軟骨基質(zhì),

24、有望成為非手術(shù)治療中、晚期OA的新型靶點13。3.2 鈣化層在OA發(fā)病機制中的作用鈣化層是骨和軟骨之間重要的界面結(jié)構(gòu),起著傳導(dǎo)應(yīng)力、抵抗剪切力、緊密連接骨軟骨和限制組織液在骨軟骨之間自由交換等作用14。本次實驗發(fā)現(xiàn)隨著OA病程延長,軟骨下骨持續(xù)增厚,而鈣化層則經(jīng)歷了一個早期增厚,中、晚期厚度逐漸減小甚至局部完全缺失的過程,具有重要意義。在OA早期,潮線處鈣化抑制機制解除15,鈣化層軟骨細胞激活表達生長板軟骨細胞表型,分泌型膠原,導(dǎo)致透明軟骨基質(zhì)礦化,潮線復(fù)制、前移,鈣化層厚度增加16,有利于抵抗骨-軟骨界面異常增加的剪切力,也有助于延緩血管侵入非鈣化軟骨。此時,鈣化層在膝內(nèi)翻所致異常應(yīng)力反復(fù)作

25、用下因疲勞出現(xiàn)微裂隙,并且異常負重的內(nèi)側(cè)平臺微裂隙數(shù)量遠高于外側(cè)平臺17;鈣化層微裂隙首先會誘發(fā)血管侵入、鈣化層重塑以修復(fù)微裂隙,微裂隙形成18和基質(zhì)不均勻礦化產(chǎn)生的鈣化層非礦化區(qū)域19還可為小分子物質(zhì)(如細胞因子等在骨軟骨之間轉(zhuǎn)運提供潛在通道。在OA中期,鈣化層繼續(xù)增厚,進一步減小非鈣化軟骨厚度,使應(yīng)力過度集中在非鈣化軟骨,加快其損傷、退變;同時,髓腔來源的血管大量侵入鈣表1脛骨內(nèi)、外側(cè)平臺軟骨和軟骨下骨結(jié)構(gòu)參數(shù)對比分析(n=30,x sTab.1 Comparison of cartilage and subchondral bone structural parameters betwe

26、en medial and lateral plateaus(n=30,x s組別GroupTAC厚度(mTAC thickness(mACC厚度(mACC thickness(mACC/TAC比值(%Ratio of ACC/TAC(%SCP厚度(mSCP thickness(mBV/TV(%內(nèi)側(cè)平臺Medial plateau883.2 304.0241.1 137.729.8 17.9767.2 192.660.9 10.1外側(cè)平臺Lateral plateau1 955.4 691.9218.1 109.312.2 7.1698.9 121.041.1 7.7統(tǒng)計值Statistic

27、t= 9.578P= 0.000t=0.850P=0.402t=6.021P=0.000t=3.114P=0.004t=15.594P= 0.000 圖1 脛骨平臺大體觀察 左側(cè)為外側(cè) 右側(cè)為內(nèi)側(cè) 紅色箭頭示血管翳樣組織 黑色箭頭示廣泛軟骨下骨暴露 圖2 番紅O/固綠染色觀察軟骨退變情況早期( 40 箭頭示淺表層斜行裂隙中期( 100 箭頭示垂直裂隙進入軟骨深層晚期( 40 箭頭示“象牙化”軟骨下骨晚期肉芽組織( 40 箭頭示肉芽組織和殘留軟骨之間界面 圖3 鈣化層和軟骨下骨病理改變?nèi)旧^察 早期 潮線結(jié)構(gòu)改變(番紅O/固綠染色 100 黑色箭頭示潮線復(fù)制 黃色箭頭示鈣化層軟骨細胞簇集 (HE

28、 100 黑色箭 頭示多發(fā)微裂隙 紅色箭頭示血管侵入鈣化層 中期1級軟骨下骨吸收陷窩(番紅O/固綠染色 200 中期2級軟骨下骨吸收陷 窩(番紅O/固綠染色 100 (番紅O/固綠染色 100 箭頭示成骨細胞, 早期軟骨下骨重 塑、增厚(番紅O/固綠染色 40中期肉芽組織(HE 100 箭頭示肉芽組織和骨髓腔相通晚期軟骨下骨囊腫形成(HE 10 晚期軟骨樣組織沉積(番紅O/固綠染色 40 Fig.1 Gross observation of the tibial plateau The left was the lateral side The right was the medial sid

29、e Red arrow indicated pannus-like tissue Black arrow indicated extensively exposed subchondral bone Fig.2 Safranin O/fast green staining observation of the uncalci ed cartilage Stage I ( 40 Arrow in-dicated oblique ssures within the super cial zone Stage II ( 100 Arrow indicated vertical ssures exte

30、nding into the deep zone III ( 40 Ar- row indicated eburnated subchondral boneStage III granulation tissues ( 40 Arrow indicated the interface between the granulation tissues and residual cartilage Fig.3 Histologic observation of the calci ed zone and subchondral boneStage I tidemark changes (Safran

31、in O/fast green staining 100 Black arrow indicated duplicated tidemark Yellow arrow indicated clustering chondrocytes within calci ed zone Stage I microcracks formation (HE 100 Black arrow indicated multiple microcracks Red arrow indicated vessels intruding calci ed zone Stage II grade 1 subchondral

32、 bone resorption pit (Safranin O/fast green staining 200Stage II grade 2 subchondral bone resorption pit (Safranin O/fast green staining 100Stage III endochondral ossi cation (Safranin O/fast green staining 100 Arrow indicated osteoblasts and surrounding new bone tissuesStage I remodeling and thicke

33、ning subchondral bone (Safranin O/fast green staining 40Stage II granulation tissues (HE 100 Arrow indicated granulation tissues connecting to the bone marrow cavityIII subchondral bone cyst formation (HE 10Stage III cartilaginous deposits (Safranin O/fast green staining 40 化層,表現(xiàn)為多發(fā)的1級或2級軟骨下骨吸收陷窩,使來

34、自病變軟骨下骨的大分子物質(zhì),如基質(zhì)金屬蛋白酶等參與調(diào)節(jié)軟骨細胞代謝8,20。在OA晚期,潮線前移、基質(zhì)礦化為軟骨內(nèi)化骨過程提供充足物質(zhì)準(zhǔn)備,鈣化層在侵入血管的作用下發(fā)生重塑,不斷向軟骨下骨轉(zhuǎn)化,鈣化層厚度減小甚至完全消失21。發(fā)生OA時鈣化層病理改變的本質(zhì)是二次骨化中心重新激活17,這一軟骨內(nèi)化骨過程離不開軟骨細胞肥大凋亡、軟骨基質(zhì)礦化和新生血管形成。利用甲狀旁腺激素抑制鈣化層中軟骨細胞終末分化、凋亡22,使用磷酸枸櫞酸鹽抑制潮線前移、基質(zhì)礦化23,應(yīng)用VEGF拮抗劑阻斷新生血管侵入鈣化層在體外和動物實驗中都起到了良好的保護軟骨、緩解OA進展作用24-25。總之,將鈣化層作為作用靶點為OA的預(yù)

35、防治療提供了新思路。3.3軟骨下骨在OA發(fā)病機制中的作用實驗結(jié)果提示,隨著OA病程進展,軟骨下骨不斷重塑、增厚,內(nèi)側(cè)平臺軟骨下骨厚度也明顯高于外側(cè)平臺;但由于軟骨下骨重塑時骨轉(zhuǎn)換率加快和血管密度升高,其硬度(彈性模量最終是減小的,因此軟骨下骨主要不是通過機械力學(xué)途徑誘發(fā)軟骨退變。體外實驗發(fā)現(xiàn)“硬化”軟骨下骨成骨細胞合成的促分解性細胞因子26、基質(zhì)金屬蛋白酶27等可能通過鈣化層微裂隙和新生血管進入非鈣化軟骨,導(dǎo)致軟骨細胞表型改變和功能異常,誘發(fā)軟骨退變、基質(zhì)崩解;反之,肥大的軟骨細胞也可進一步誘導(dǎo)成骨細胞異常分化,形成惡性循環(huán),加快OA進展28。OA動物模型研究表明,早期應(yīng)用降鈣素29或二磷酸鹽

36、30等骨吸收抑制劑,可阻斷破骨細胞動員,從而終止繼發(fā)成骨細胞激活,降低骨轉(zhuǎn)化率,防止軟骨下骨重塑,起到保護軟骨的作用,說明軟骨下骨主要通生物化學(xué)途徑誘發(fā)OA。MRI研究表明軟骨下骨骨髓損傷信號(bone marrow lesions, BMLs可位點特異性的導(dǎo)致其上方軟骨退變31,而局部BMLs病檢主要表現(xiàn)為軟骨下骨重塑、增厚、硬度下降和高轉(zhuǎn)化率狀態(tài)32。一項前瞻性臨床研究發(fā)現(xiàn),自體軟骨移植遠期療效不如自體骨軟骨移植(馬賽克技術(shù)的原因可能就在于后者去除了病變的軟骨下骨33。根據(jù)Wolff定律,骨小梁不斷增厚以適應(yīng)平臺應(yīng)力異常增大,是一種繼發(fā)的適應(yīng)性改變。關(guān)節(jié)滑液通過鈣化層微裂隙和血管進入髓腔,

37、隨之骨內(nèi)壓升高、骨小梁凹陷可能是OA晚期軟骨下骨囊腫形成的原因34。軟骨下骨高轉(zhuǎn)化率導(dǎo)致軟骨樣組織沉積在骨小梁中,其形成和轉(zhuǎn)歸機制尚不清楚,可能是裸露軟骨下骨一種自發(fā)性修復(fù)反應(yīng)35。綜上述,軟骨和軟骨下骨是一個相互依賴、不可分割的功能單位。隨著軟骨下骨病變的進展,軟骨退變程度也更為嚴重;軟骨下骨重塑不是一種簡單的繼發(fā)反應(yīng),而是和軟骨退變密切相關(guān)。鈣化層二次骨化中心激活和軟骨下骨高轉(zhuǎn)化率在OA起始和進展中具有重要的作用,軟骨和軟骨下骨通過鈣化層介導(dǎo)發(fā)生相互作用,形成惡性循環(huán),貫穿OA病程始終36。深入研究鈣化層和軟骨下骨的結(jié)構(gòu)、功能及其在OA發(fā)病機制中的作用,將為臨床預(yù)防和治療OA開辟了嶄新的道

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