華秉譞(綜述) 閻作勤(審校)

(復(fù)旦大學(xué)附屬中山醫(yī)院骨科 上海 200032)

骨關(guān)節(jié)炎軟骨下骨的變化及其分子機(jī)制的研究進(jìn)展

華秉譞(綜述) 閻作勤△(審校)

(復(fù)旦大學(xué)附屬中山醫(yī)院骨科 上海 200032)

骨關(guān)節(jié)炎(osteoarthritis,OA)是一種最常見的慢性骨關(guān)節(jié)疾病,可累及整個(gè)關(guān)節(jié)。軟骨下骨作為關(guān)節(jié)的重要組成部分,與OA的發(fā)生發(fā)展密切相關(guān)。OA中軟骨下骨變化的機(jī)制復(fù)雜,目前尚未完全闡明。本文通過(guò)文獻(xiàn)回顧對(duì)OA中軟骨下骨的病理變化,OPG/RANKL/RANK系統(tǒng)、轉(zhuǎn)化生長(zhǎng)因子β (transforming growth factor β,TGFβ)、雌激素-雌激素受體信號(hào)通路和脂代謝等因素對(duì)軟骨下骨的影響進(jìn)行綜述,探討OA中軟骨下骨變化的作用及其分子機(jī)制。

骨關(guān)節(jié)炎; 軟骨下骨; OPG/RANKL/RANK系統(tǒng); TGFβ; 雌激素; 雌激素受體; 脂代謝

骨關(guān)節(jié)炎(osteoarthritis,OA)是一種常見的慢性骨關(guān)節(jié)疾病,是造成關(guān)節(jié)疼痛和功能障礙的重要原因之一[1]。OA好發(fā)于中老年患者,女性多于男性,60歲以上的人群中患病率可達(dá)50%,75歲以上的人群中則可達(dá)到80%,該病的致殘率高達(dá)53%。OA多發(fā)于負(fù)重大、活動(dòng)多的關(guān)節(jié),如膝、脊柱(頸椎和腰椎)、髖、踝、手等關(guān)節(jié)[2-3]。原發(fā)性O(shè)A的病因尚不明確,除年齡外[4-5],還與免疫、生物學(xué)等多種因素相關(guān)[6-7]。

OA主要病理變化發(fā)生在軟骨、軟骨下骨與滑膜[8]。過(guò)去研究的重點(diǎn)主要集中在關(guān)節(jié)軟骨,近年來(lái)軟骨下骨對(duì)于關(guān)節(jié)軟骨的重要作用逐漸被重視[9]。自Radin等[10]于1972年首次提出軟骨下骨改變是OA發(fā)病啟動(dòng)因素的假說(shuō)后,近年來(lái)越來(lái)越多的研究表明,軟骨下骨確實(shí)在OA病變中起到重要作用[11-14],有學(xué)者認(rèn)為軟骨下骨硬化是OA軟骨病變的起始因素[15]。OA中軟骨下骨的變化及其分子機(jī)制也成為了當(dāng)前研究的熱點(diǎn),本文就此作一綜述。

OA中軟骨下骨的病理及超微結(jié)構(gòu)變化 軟骨下骨是組成關(guān)節(jié)的重要部分,主要包括軟骨下皮質(zhì)終板、骨小梁結(jié)構(gòu)、血管及小梁間隙結(jié)構(gòu),主要生物學(xué)功能為吸收應(yīng)力、緩沖震蕩以及維持關(guān)節(jié)形狀等,還能為軟骨提供營(yíng)養(yǎng)及清除代謝產(chǎn)物[16]。王華偉[17]通過(guò)HE、番紅O/固綠、馮庫(kù)薩、甲苯胺藍(lán)、天狼猩紅等多種染色,觀察了21例臨床診斷原發(fā)性O(shè)A的股骨髁標(biāo)本,獲得的病理學(xué)結(jié)果顯示:原發(fā)性O(shè)A的骨軟縱斷面三層結(jié)構(gòu)顯示不清,潮線斷裂、間隙增寬、鈣化軟骨層增厚。關(guān)節(jié)主要病理組織學(xué)改變包括:(1)三層結(jié)構(gòu)潮線復(fù)制、漂移; (2)鈣化層增厚,伴血管長(zhǎng)入;(3)非鈣化軟骨及鈣化層纖維樣改變;(4)潮線間隙增寬;(5)深層軟骨及鈣化層缺損。李西海等[18]通過(guò)建立大鼠膝關(guān)節(jié)OA模型,發(fā)現(xiàn)OA膝關(guān)節(jié)的軟骨表面粗糙,完整性破壞,表層軟骨出現(xiàn)纖維化變性及軟骨缺損,甚至軟骨下骨裸露,軟骨下骨致密層變薄,骨松質(zhì)層骨小梁稀疏,硬化或囊變,邊緣有丘狀隆起的骨贅。Yan等[19]在DH豚鼠與年齡相關(guān)的OA模型中,通過(guò)掃描電鏡和透射電鏡分別觀察了1、3、6、9、12月齡的DH豚鼠,觀察到關(guān)節(jié)軟骨會(huì)隨著OA的進(jìn)展逐漸出現(xiàn)微纖毛、軟骨表面潰瘍、膠原纖維退化等變化,軟骨細(xì)胞也會(huì)隨著OA進(jìn)展逐漸出現(xiàn)形態(tài)的不規(guī)則以及細(xì)胞凋亡,軟骨細(xì)胞的細(xì)胞質(zhì)、細(xì)胞核會(huì)逐漸出現(xiàn)溶解和固縮。研究表明軟骨下骨與軟骨之間的緊密連接在關(guān)節(jié)活動(dòng)和保護(hù)功能中起到重要的作用[20-21]。

OA軟骨下骨重建及硬化 OA骨端發(fā)生的病理變化主要包括骨重建及骨質(zhì)硬化,包含軟骨下骨密度增高、骨量增加。骨重建是指骨組織的形態(tài)和密度隨著生物力學(xué)環(huán)境的改變而改變的生理行為,載荷高的地方骨的質(zhì)量和密度增高,反之骨的質(zhì)量和密度發(fā)生下降。正常生理情況下,骨重建是通過(guò)成骨細(xì)胞和破骨細(xì)胞來(lái)調(diào)節(jié)的,成骨細(xì)胞負(fù)責(zé)骨基質(zhì)的合成、分泌和礦化,破骨細(xì)胞具有骨吸收功能,兩者作用互相拮抗、互相平衡,它們的活化和凋亡在骨骼的生長(zhǎng)發(fā)育中起重要作用。

OA的早期病理變化主要表現(xiàn)為骨吸收增強(qiáng),破骨細(xì)胞溶骨作用增強(qiáng),軟骨下骨骨質(zhì)疏松,骨量減少,骨小梁變薄。Intema等[22]利用狗前交叉韌帶切斷和內(nèi)側(cè)半月板切除的方法復(fù)制OA模型,通過(guò)觀察組織學(xué)以及影像學(xué)超微結(jié)構(gòu)發(fā)現(xiàn),早期OA關(guān)節(jié)軟骨蛋白聚糖丟失增多,軟骨下骨厚度降低,骨小梁厚度及體積均下降。晚期軟骨下骨骨形成增加,發(fā)生硬化。Ham等[23]通過(guò)卵巢切除的成年母猴復(fù)制OA模型,發(fā)現(xiàn)雌激素替代治療(estrogen replacement therapy,ERT)的實(shí)驗(yàn)組發(fā)生OA的概率顯著低于無(wú)雌激素治療的對(duì)照組,對(duì)比骨形態(tài)組織計(jì)量發(fā)現(xiàn)OA晚期骨小梁厚度增加,新生骨組織礦化升高,骨形成率增加,軟骨下骨骨密度增高,發(fā)生硬化。軟骨下骨的硬化可導(dǎo)致其吸收應(yīng)力、緩沖震蕩的作用減少,從而加劇了關(guān)節(jié)的損害及退變[24]。軟骨下骨的損害還可加重軟骨的病變[12,25]。同時(shí),OA晚期關(guān)節(jié)微血管形成增加,并且浸潤(rùn)到軟骨下骨,也可通過(guò)表達(dá)基質(zhì)金屬蛋白酶(matrix metalloproteinase,MMP)加劇軟骨的退化,從而加重OA病情[26-27]。隨著OA病情的加重,則會(huì)出現(xiàn)上述典型的病理及超微結(jié)構(gòu)的變化及相關(guān)的臨床表現(xiàn)。

調(diào)控OA中軟骨下骨變化的分子機(jī)制

OPG/RANKL/RANK系統(tǒng)的作用 2000年,美國(guó)骨與礦物質(zhì)協(xié)會(huì)最早提出骨保護(hù)素(osteoprotegerin,OPG)、核因子κB受體活化因子(receptor activator for nuclear factor-κB,RANK)、RANK配體(receptor activator for nuclear factor-κB ligand,RANKL)是緊密聯(lián)系的整體,命名為OPG/RANKL/RANK系統(tǒng)[28]。RANK是唯一已知的RANKL發(fā)揮作用的受體,兩者結(jié)合后激活信號(hào)通路,使破骨細(xì)胞前體分化,促使破骨細(xì)胞成熟,發(fā)揮骨吸收作用;OPG是抑制骨吸收的細(xì)胞因子,其功能是阻斷RANK與RANKL的結(jié)合,抑制破骨細(xì)胞的成熟,從而抑制其骨吸收作用[29-30]。

OA中OPG/RANKL/RANK系統(tǒng)對(duì)于軟骨下骨起到重要作用。Kwan Tat等[31]證實(shí),OA軟骨下骨中OPG水平降低,RANKL在早期OA中表達(dá)增加,在晚期OA中表達(dá)減少。軟骨下骨破骨細(xì)胞的激活在OA的起始病變中起到重要的作用[32],而OPG/RANKL比值可以作為反映破骨細(xì)胞活動(dòng)水平的一個(gè)指標(biāo),調(diào)控骨代謝[33]。OPG/RANKL比值與軟骨下骨厚度成正比,在早期OA中OPG/RANKL比值降低,破骨細(xì)胞活性增強(qiáng),致使骨吸收增加,軟骨下骨發(fā)生異常重建;而在晚期OA中該比值上升,破骨細(xì)胞活性降低,此時(shí)骨形成增加,導(dǎo)致骨質(zhì)硬化、形成骨贅等。Martinez-Calatrava等[34]和Moreno-Rubio等[35]研究發(fā)現(xiàn),OA中不僅軟骨細(xì)胞高表達(dá)RANKL,細(xì)胞外基質(zhì)中也可以發(fā)現(xiàn)RANKL,并作用于軟骨下骨,造成骨丟失。Funck-Brentano等[32]在半月板切除誘導(dǎo)OA小鼠模型中,將小鼠軟骨下骨上清液加入到軟骨組織中,發(fā)現(xiàn)軟骨代謝中的蛋白多糖和蛋白聚糖釋放減少,提示骨分泌的可溶性因子參與調(diào)節(jié)軟骨代謝[36],這種細(xì)胞因子和信號(hào)傳導(dǎo)通路可能通過(guò)軟骨下骨新生血管以及局部骨裂隙及鈣化軟骨中的微管進(jìn)行傳導(dǎo)。由此說(shuō)明OPG和RANKL參與關(guān)節(jié)軟骨和骨之間的雙向調(diào)節(jié),包括軟骨代謝和軟骨下骨吸收,表明OPG/RANKL/RANK系統(tǒng)在OA中的重要性。

TGF-β信號(hào)通路的作用 轉(zhuǎn)化生長(zhǎng)因子β(transforming growth factor β,TGFβ)屬于一類促進(jìn)細(xì)胞生長(zhǎng)和轉(zhuǎn)化的細(xì)胞因子超家族,有6種不同亞型,其中TGFβ1、TGFβ2和TGFβ3亞型表達(dá)于哺乳動(dòng)物[37-38],是維持關(guān)節(jié)軟骨代謝平衡與結(jié)構(gòu)完整性的重要因素之一[39]。Zhen等[40]通過(guò)切斷大鼠前交叉韌帶制作OA模型,發(fā)現(xiàn)機(jī)械應(yīng)力改變軟骨下骨形態(tài)并導(dǎo)致軟骨下骨TGFβ濃度升高,同樣在膝關(guān)節(jié)OA患者軟骨下骨TGFβ濃度也明顯升高;而在動(dòng)物模型中,在軟骨下骨加入適量的TGFβI型受體抑制劑(TβRI)可以穩(wěn)定軟骨下骨結(jié)構(gòu)(劑量過(guò)大會(huì)導(dǎo)致關(guān)節(jié)軟骨蛋白多糖丟失),防止OA中關(guān)節(jié)軟骨的退化。此外,TGFβ可以誘導(dǎo)骨髓間充質(zhì)干細(xì)胞(bone marrow stem cell,BMSC)的遷移聚集,從而導(dǎo)致異常骨重塑[41],促進(jìn)OA的病理進(jìn)展。使用TβRI可以減少骨重塑,為OA治療提供新的思路[40]。骨形成總是伴隨著血管生成,TGFβ可以通過(guò)影響內(nèi)皮祖細(xì)胞以及促進(jìn)間充質(zhì)干細(xì)胞的旁分泌機(jī)制來(lái)促進(jìn)血管生成[42-43],抑制 TGFβ 的活性,減少血管生成可以減少TGFβ相關(guān)異常骨形成。Yusup等[44]通過(guò)對(duì)40例晚期膝關(guān)節(jié)OA患者行磁共振、血清細(xì)胞因子及組織學(xué)檢查,發(fā)現(xiàn)滑膜血管組織TGFβ水平與軟骨下骨髓病變、軟骨下骨囊腫、軟骨下骨磨損程度呈正相關(guān)。Jiao等[45]使用TGFβ1轉(zhuǎn)基因CED小鼠模型,使TGFβ1在骨髓中高表達(dá),導(dǎo)致下頜髁軟骨下骨異常骨重建,進(jìn)而出現(xiàn)軟骨的異常,表明TGFβ在顳下頜關(guān)節(jié)骨關(guān)節(jié)炎的發(fā)展中起到重要作用。

TGFβ對(duì)于軟骨下骨微環(huán)境的調(diào)控也影響著OA的進(jìn)展,TGFβ通過(guò)調(diào)節(jié)BMSC的分化募集,形成骨樣小島,導(dǎo)致異常骨重塑[41,46];可以介導(dǎo)上皮間質(zhì)轉(zhuǎn)化(epithelial-mesenchymal transition,EMT)及內(nèi)皮間質(zhì)轉(zhuǎn)化(endothelial-mesenchymal transition,EndoMT)通路,為OA軟骨下骨血管生成增加提供上皮細(xì)胞和內(nèi)皮細(xì)胞的資源[47-49]。二膦酸鹽類治療OA的研究已有很長(zhǎng)一段時(shí)間[50],其中阿侖膦酸鈉對(duì)于OA的治療被認(rèn)為是一項(xiàng)重要的發(fā)現(xiàn),它不但保護(hù)軟骨對(duì)于應(yīng)力的變化,還可以保護(hù)軟骨下骨對(duì)于應(yīng)力的變化,在切斷兔前交叉韌帶復(fù)制的OA模型中,阿侖膦酸鈉可以防止關(guān)節(jié)區(qū)域骨丟失,抑制破骨細(xì)胞向軟骨下骨區(qū)域募集[51]。阿侖膦酸鈉可以抑制早期軟骨下骨吸收和防止異常骨贅形成,這一效果可以用減少局部TGFβ的活化來(lái)解釋[52]。鑒于TGFβ在OA的病理過(guò)程中起到重要作用,特異性抑制軟骨下骨TGFβ活性也給OA的治療提供了新的臨床思路。

雌激素-雌激素受體信號(hào)通路的作用 雌激素是人體內(nèi)分泌的重要激素之一。流行病學(xué)調(diào)查顯示,雌激素減退有增加OA患病的可能[53],女性O(shè)A發(fā)病率高于男性,特別是在絕經(jīng)以后[54],一項(xiàng)研究表明64%的女性膝關(guān)節(jié)OA或出現(xiàn)相關(guān)OA癥狀者在5年內(nèi)絕經(jīng)或者接受子宮切除術(shù)[55]。絕經(jīng)后女性比同齡男性更易出現(xiàn)髖、膝OA癥狀,且病程進(jìn)展更快[56]。雌激素受體(estrogen receptor,ER)分為ER-α和ER-β兩種亞型,此兩型受體在軟骨細(xì)胞、軟骨下骨細(xì)胞、滑膜細(xì)胞和韌帶成纖維細(xì)胞中均有表達(dá),說(shuō)明關(guān)節(jié)組織是雌激素的作用目標(biāo)之一[57-60]。雌激素對(duì)于關(guān)節(jié)穩(wěn)定起到重要的保護(hù)作用。在動(dòng)物模型中,卵巢切除會(huì)引起強(qiáng)烈的軟骨下骨丟失和重建,削弱軟骨下骨小梁生物力學(xué)性能,隨之會(huì)導(dǎo)致軟骨的損傷[55,61-62]。Sniekers等[63]敲除雌性小鼠的雌激素受體基因,導(dǎo)致小鼠脛骨骨贅增加、軟骨下骨板變薄,發(fā)生了OA早期的病變。通過(guò)切除母猴卵巢可復(fù)制OA模型,ERT的實(shí)驗(yàn)組發(fā)生OA的概率顯著低于對(duì)照組,表明雌激素對(duì)于維持關(guān)節(jié)骨量和功能的重要作用[23],ERT對(duì)于OA有一定治療作用,可延緩OA發(fā)展[64]。一項(xiàng)大樣本量臨床分析表明,激素替代治療(hormone replacement therapy,HRT)可以顯著減少OA患者關(guān)節(jié)置換術(shù)后翻修的概率,提示HRT對(duì)于OA關(guān)節(jié)置換的積極效果[65]。選擇性雌激素受體調(diào)節(jié)劑(selective estrogen receptor modulators,SERMs)被多次報(bào)道對(duì)于OA治療有益,并且已經(jīng)在歐美市場(chǎng)上使用[66],相較于對(duì)于軟骨的短期作用,SERMs對(duì)于軟骨下骨的作用是長(zhǎng)期的[64]。也有學(xué)者認(rèn)為,過(guò)高水平的雌激素不利于關(guān)節(jié)穩(wěn)態(tài),會(huì)誘發(fā)關(guān)節(jié)損傷,因?yàn)楦邉┝康拇萍に卦黾覫L-1β誘導(dǎo)的蛋白聚糖降解和MMP的生成而損害關(guān)節(jié)軟骨[54,67]。

雌激素及其受體在分子水平上可調(diào)節(jié)一系列細(xì)胞因子。雌激素可上調(diào)OPG表達(dá)[68],體外實(shí)驗(yàn)證實(shí)雌激素可以誘導(dǎo)OPG產(chǎn)生[69]。同時(shí),雌激素可以抑制RANKL的作用,通過(guò)抑制破骨細(xì)胞的作用而影響骨代謝[70-71]。另外,在卵巢切除小鼠中TGFβ表達(dá)下降,說(shuō)明內(nèi)源性雌激素缺乏可能直接抑制成骨活性[72]。

脂代謝的作用 OA被認(rèn)為是一項(xiàng)和年齡及代謝相關(guān)的疾病[73-74],長(zhǎng)期以來(lái)肥胖被認(rèn)為是導(dǎo)致OA的高危因素之一[75],與肥胖密切相關(guān)的脂代謝被認(rèn)為在OA發(fā)病中起重要作用[76-77]。Chaput等[78]通過(guò)對(duì)OA患者和健康者股骨標(biāo)本的蛋白組學(xué)研究發(fā)現(xiàn),在OA患者中載脂蛋白A-I顯著下降。張榮凱等[79]以大鼠前交叉韌帶切斷和內(nèi)側(cè)半月板切除復(fù)制OA模型,通過(guò)基因芯片篩查研究早期OA軟骨下骨脂蛋白相關(guān)基因的表達(dá)情況,發(fā)現(xiàn)多種脂蛋白相關(guān)基因在術(shù)后1個(gè)月內(nèi)發(fā)生變化。瘦素、脂聯(lián)素、內(nèi)脂素和抵抗素作為脂肪組織釋放的脂肪因子被認(rèn)為在OA軟骨和骨的動(dòng)態(tài)平衡中發(fā)揮重要作用[77]。Mutabaruka等[80]通過(guò)臨床研究和尸體解剖發(fā)現(xiàn),在OA患者膝關(guān)節(jié)軟骨下骨中瘦素顯著增加,并通過(guò)調(diào)節(jié)堿性磷酸酶、骨鈣素、Ⅰ型膠原蛋白和TGF-β1水平完成促進(jìn)異常成骨細(xì)胞的分化,從而導(dǎo)致OA晚期異常骨贅的產(chǎn)生。Berry等[81]通過(guò)一項(xiàng)為期2年的隨訪發(fā)現(xiàn),OA患者瘦素水平的增加與骨形成標(biāo)志物骨鈣素和I型前膠原N末端前肽呈正相關(guān)。體外研究表明,脂聯(lián)素通過(guò)增加RANKL表達(dá)和抑制OPG表達(dá)增加破骨細(xì)胞的形成[82],而在骨贅生成中脂聯(lián)素的水平較低,提示其與早期骨贅生成的相關(guān)性[77]。Choe等[83]發(fā)現(xiàn)血清抵抗素水平與手OA影像學(xué)軟骨下侵蝕程度呈正相關(guān)。Wang等[84]通過(guò)OA患者和正常人的特殊磁共振序列掃描發(fā)現(xiàn),OA患者脛骨軟骨下骨脂質(zhì)的影像學(xué)變化,可能與OA軟骨下骨髓水腫相關(guān)。脂代謝相關(guān)疾病如動(dòng)脈粥樣硬化的發(fā)生也與OA的發(fā)生有一定的聯(lián)系,可能的機(jī)制是代謝性疾病造成的軟骨下骨代謝障礙以及由脂肪因子引起的系統(tǒng)性炎性反應(yīng),從而導(dǎo)致OA病理生理作用[85-87]。當(dāng)前,更多的研究表明,脂代謝及脂肪因子對(duì)于OA軟骨細(xì)胞具有重要的作用,主要是通過(guò)增加關(guān)節(jié)軟骨細(xì)胞和滑膜成纖維細(xì)胞促炎介質(zhì)的產(chǎn)生,炎性介質(zhì)和細(xì)胞因子誘導(dǎo)了關(guān)節(jié)局部炎性因子及軟骨基質(zhì)裂解酶的產(chǎn)生,在OA炎癥產(chǎn)生、軟骨破壞過(guò)程中發(fā)揮著重要作用[88-89]。瘦素通過(guò)轉(zhuǎn)錄因子NF-κB、蛋白激酶(protein kinase C,PKC)和絲裂原活化蛋白A激酶(mitogen-activated protein kinase,MAPK)信號(hào)通路[90-91],而脂聯(lián)素是通過(guò)腺苷酸活化蛋白激酶(adenosine 5′-monophosphate-activated protein kinase,AMPK)及c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)信號(hào)通路分別誘導(dǎo)NO和MMP引起炎性反應(yīng)[88,92]。瘦素等脂肪因子對(duì)于軟骨下骨的作用機(jī)制目前仍未完全明確,可能是通過(guò)引起局部的炎性反應(yīng)導(dǎo)致軟骨下骨內(nèi)環(huán)境的變化。軟骨是一種無(wú)血管組織,軟骨下骨的代謝不僅作用于其本身,還通過(guò)分子擴(kuò)散直接影響軟骨[93],繼而引發(fā)OA的病變,但其機(jī)制及通路仍有待進(jìn)一步研究。脂代謝導(dǎo)致軟骨下骨內(nèi)環(huán)境的變化,進(jìn)而影響自身和軟骨代謝,在OA的發(fā)生發(fā)展中起到一定的作用。

結(jié)語(yǔ) OA中軟骨下骨的變化被日漸重視,但究竟是軟骨下骨的變化引起關(guān)節(jié)軟骨的病變還是軟骨病變影響軟骨下骨這一問題至今學(xué)界仍無(wú)定論?？梢悦鞔_的是,軟骨下骨在OA的發(fā)生發(fā)展中扮演重要的角色,OPG/RANKL/RANK系統(tǒng)、TGFβ、雌激素-雌激素受體信號(hào)通路和脂代謝等因素均對(duì)OA軟骨下骨起到重要的作用,引起軟骨下骨內(nèi)環(huán)境改變和病理變化,也會(huì)對(duì)軟骨代謝和軟骨細(xì)胞起到影響,從而導(dǎo)致OA的發(fā)生發(fā)展。OA診斷主要依靠X線攝片,并被認(rèn)為是金標(biāo)準(zhǔn)。目前對(duì)于OA尚無(wú)可以治愈疾病的藥物,只能從癥狀上緩解病情。明確OPG/RANKL/RANK系統(tǒng)、TGFβ、雌激素-雌激素受體信號(hào)通路和脂代謝等因素在OA中對(duì)于軟骨下骨及整個(gè)關(guān)節(jié)軟骨的作用,可以為OA的早期診斷和治療提供新的思路和方法。

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Research progress on the changes of subchondral bone in osteoarthritis and its molecular mechanisms

HUA Bing-xuan, YAN Zuo-qin△

(DepartmentofOrthopaedics,ZhongshanHospital,FudanUniversity,Shanghai200032,China)

Osteoarthritis (OA) is one of the most common chronic osteoarthritic diseases,which can involve the whole joint.Subchondral bone is an important part of the joint and has a close relationship to the development of OA.The changes and mechanisms of subchondral bone in OA are complex and remain disputes.In this review,we will discuss the advances of the molecular mechanisms of subchondral bone in OA,which include the pathological changes and the roles of the OPG/RANKL/RANK system,transforming growth factor β (TGFβ),estrogen-estrogen receptors and lipid metabolism in OA.

osteoarthritis; subchondral bone; OPG/RANKL/RANK system; TGFβ; estrogen; estrogen receptors; lipid metabolism

R684.3

B

10.3969/j.issn.1672-8467.2017.02.018

2016-05-06;編輯:段佳)

△Corresponding author E-mail:yan1002@hotmail.com