半乳糖凝集素‑3对骨关节炎成骨细胞矿化的作用研究

doi:10.19586/j.2095-2341.2021.0031

生物技术进展 ›› 2021, Vol. 11 ›› Issue (6): 802-806.DOI: 10.19586/j.2095-2341.2021.0031

半乳糖凝集素‑3对骨关节炎成骨细胞矿化的作用研究

胡勇(), 杨俭(), 邱波

武汉大学人民医院骨科，武汉 430060

收稿日期:2021-03-09 接受日期:2021-06-28 出版日期:2021-11-25 发布日期:2021-11-26
通讯作者: 杨俭
作者简介:胡勇 E-mail：hyrm2017@126.com；
基金资助:
国家自然科学基金项目(82002337)

The Effect of Galectin‑3 on the Abnormal Mineralization of Osteoarthritic Osteoblasts

Yong HU(), Jian YANG(), Bo QIU

Department of Orthopaedics，Renmin Hospital of Wuhan University，Wuhan 430060，China

Received:2021-03-09 Accepted:2021-06-28 Online:2021-11-25 Published:2021-11-26
Contact: Jian YANG

摘要/Abstract

摘要：

炎症反应以炎症因子为代表，是骨关节炎（osteoarthritis，OA）中软骨下骨发生病变的重要机制。炎症因子半乳糖凝集素?3（galectin?3，Gal?3）会引起软骨下骨OA样变，但机制尚不清楚。利用因膝关节OA行全膝关节置换患者的胫骨平台标本，培养成骨细胞。分别在正常氧和缺氧条件下用Gal?3处理成骨细胞后，检测骨钙素、ERRα和Sirtuin 1的表达情况。同时，给予矿化液培养的成骨细胞以Gal?3处理，28 d后使用茜素红染色检测成骨细胞矿化程度并进行定量分析。结果显示，Gal?3抑制成骨细胞骨钙素的表达，在缺氧条件下诱导ERRα和Sirtuin1的表达，在正常氧条件下Gal?3促进OA成骨细胞的矿化。正常氧条件下，Gal?3可以诱导OA成骨细胞的异常矿化，缺氧条件下Gal?3促进成骨，表明Gal?3在OA成骨细胞的矿化中扮演重要角色。

关键词: 半乳糖凝集素?3, 骨关节炎, 成骨细胞, 矿化

Abstract:

Inflammation is represented by inflammatory factors， which is an important mechanism for the pathogenesis of subchondral bone in osteoarthritis （OA）. The inflammatory factor galectin?3 （Gal?3） can induce OA lesions of subchondral bone， but the mechanism is still unclear. We used tibial plateau specimens from patients who received total knee arthroplasty due to knee joint OA to culture osteoblasts. After treating osteoblasts with Gal?3 under normoxia and hypoxia， respectively， the expression of osteocalcin， ERRα and Sirtuin1 were detected. Meanwhile， the osteoblasts cultured in the mineralization solution were treated with Gal?3， and after 28 days， the degree of mineralization of osteoblasts was detected by alizarin red staining and quantitative analysis was performed. The results showed that Gal?3 inhibited the expression of osteocalcin in osteoblasts， induced the expression of ERRα and Sirtuin1 under hypoxic conditions， and Gal?3 promoted the mineralization of OA osteoblasts under normal oxygen conditions. Under normal oxygen conditions， Gal?3 can induce abnormal mineralization of OA osteoblasts， and under hypoxic conditions Gal?3 promotes osteogenesis， indicating that Gal?3 plays an important role in the mineralization of OA osteoblasts.

Key words: galectin?3, osteoarthritis, osteoblast, mineralization

中图分类号:

Q441

胡勇, 杨俭, 邱波. 半乳糖凝集素‑3对骨关节炎成骨细胞矿化的作用研究[J]. 生物技术进展, 2021, 11(6): 802-806.

Yong HU, Jian YANG, Bo QIU. The Effect of Galectin‑3 on the Abnormal Mineralization of Osteoarthritic Osteoblasts[J]. Current Biotechnology, 2021, 11(6): 802-806.

图/表 4

表1 qRT?PCR引物序列

Table 1 Primer sequences for qRT?PCR

基因		引物序列（5'→3'）
RP29	S	5'‑GGGTCACCAGCAGCTGTACT‑3'
RP29	AS	5'‑CCGATATCCTTCGCGTACTG‑3'
Osteocalcin	S	5'‑CATGAGAGCCCTCACA‑3'
Osteocalcin	AS	5'‑AGAGCGACACCCTAGAC‑3'
ERRα	S	5'‑GGCTTTGGCCCTATCTTTTC‑3'
ERRα	AS	5'‑GGATAAGGTCAGGATGGGGT‑3'
Sirt 1	S	5'‑CGGATTAAAATTTGAGTTGTTTC‑3'
Sirt 1	AS	5'‑CCTTCCTCTTTATAACGAACGTA‑3'

图1 常氧和缺氧条件下Gal?3对矿化相关基因表达的影响A：常氧；B：缺氧。*表示与空白对照组比较，在P<0.05水平上差异具有统计学意义。

Fig.1 Effect of Gal?3 on the expression of mineralization?related genes under normoxia and hypoxia conditions

图2 不同浓度Gal?3作用下成骨细胞矿化程度的评估A~C：Gal?3作用下成骨细胞矿化茜素红染色大体观。A:空白对照组矿化染色；B:Gal?3（1.5 μg·mL-1）处理组矿化染色；C:Gal?3（5 μg·mL-1）处理组矿化染色。D~I：Gal?3作用下成骨细胞矿化茜素红染色镜下观。D、G:空白对照组矿化染色（í20、í100）；E、H:Gal?3（1.5 μg·mL-1）处理组矿化染色（í20、í100）；F、I:Gal?3（5 μg·mL-1）处理组矿化染色（í20、í100）。

Fig.2 Evaluation of the degree of mineralization of osteoblasts under different concentrations of Gal?3

图3 不同浓度Gal?3作用下成骨细胞矿化的定量评估

Fig.3 Quantitative assessment of osteoblast mineralization under different concentrations of Gal?3

参考文献 23

1	中华医学会骨科学分会关节外科学组.骨关节炎诊疗指南(2018年版)[J].中华骨科杂志,2018,38(12):705-715.
2	HUNTER D J, BIERMA-ZEINSTRA S. Osteoarthritis[J]. Lancet, 2019, 393(10182): 1745-1759.
3	ROBINSON W H, LEPUS C M, WANG Q, et al.. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis [J]. Nat. Rev. Rheumatol., 2016, 12(10): 580-592.
4	JANELLE-MONTCALM A, BOILEAU C, POIRIER F, et al.. Extracellular localization of galectin-3 has a deleterious role in joint tissues[J]. Arthritis Res. Ther., 2007, 9(1): R20-R28.
5	LOESER R F, COLLINS J A, DIEKMAN B O. Ageing and the pathogenesis of osteoarthritis [J]. Nat. Rev. Rheumatol., 2016, 12(7): 412-420.
6	HÜGLE T, GEURTS J. What drives osteoarthritis?-synovial versus subchondral bone pathology[J]. Rheumatology, 2017, 56(9): 1461-1471.
7	HUSSAIN S M, DAWSON C, WANG Y, et al.. Vascular pathology and osteoarthritis: A systematic review[J]. J. Rheumatol., 2020, 47(5): 748-760.
8	ALTMAN R, ASCH E, BLOCH D, et al.. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association[J]. Arthritis. Rheum.., 1986, 29(8): 1039-1049.
9	ABED E, BOUVARD B, MARTINEAU X, et al.. Elevated hepatocyte growth factor levels in osteoarthritis osteoblasts contribute to their altered response to bone morphogenetic protein-2 and reduced mineralization capacity[J]. Bone, 2015, 75: 111-119.
10	HU Y, LIU Y, LAJEUNESSE D, et al.. Identification of two populations of osteoarthritic osteoblasts according to the 1,25[OH]₂ vitamin D₃ potency to stimulate osteocalcin[J]. Biomed. Mater. Eng., 2015, 25(1): 103-110.
11	BURR D B, GALLANT M A. Bone remodelling in osteoarthritis [J]. Nat. Rev. Rheumatol., 2012, 8(11): 665-673.
12	IACOBINI C, FANTAUZZI C B, PUGLIESE G, et al.. Role of galectin-3 in bone cell differentiation, bone pathophysiology and vascular osteogenesis[J]. Int. J. Mol. Sci., 2017, 18(11): 2481-2501.
13	SIMON D, DERER A, ANDES F T, et al.. Galectin-3 as a novel regulator of osteoblast-osteoclast interaction and bone homeostasis [J]. Bone, 2017, 105: 35-41.
14	IACOBINI C, BLASETTI FANTAUZZI C, BEDINI R, et al.. Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice[J]. Metabolism, 2018, 83: 149-158.
15	ALLISTON T, HERNANDEZ C J, FINDLAY D M, et al.. Bone marrow lesions in osteoarthritis: what lies beneath [J]. J. Orthop. Res., 2018, 36(7): 1818-1825.
16	TATEIWA D, YOSHIKAWA H, KAITO T. Cartilage and bone destruction in arthritis: pathogenesis and treatment strategy: a literature review[J]. Cells, 2019, 8(8): 818-849.
17	ZOCH M L, CLEMENS T L, RIDDLE R C. New insights into the biology of osteocalcin [J]. Bone, 2016, 82: 42-49.
18	MARUOTTI N, CORRADO A, CANTATORE F P. Osteoblast role in osteoarthritis pathogenesis [J]. J. Cell Physiol., 2017, 232(11): 2957-2963.
19	CHANG J, JACKSON S G, WARDALE J, et al.. Hypoxia modulates the phenotype of osteoblasts isolated from knee osteoarthritis patients, leading to undermineralized bone nodule formation[J]. Arthritis Rheumatol., 2014, 66(7): 1789-1799.
20	AULD K L, BERASI S P, LIU Y, et al.. Estrogen-related receptor alpha regulates osteoblast differentiation via Wnt/beta-catenin signaling[J]. J. Mol. Endocrinol., 2012, 48(2): 177-191.
21	CARNESECCHI J, VANACKER J M. Estrogen-related receptors and the control of bone cell fate[J]. Mol. Cell Endocrinol., 2016, 432: 37-43.
22	ZAINABADI K, LIU C J, CALDWELL A L M, et al.. SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis[J/OL]. PLoS ONE, 2017, 12(9): e0185236[2021-10-08]. .
23	ALMEIDA M, PORTER R M. Sirtuins and FoxOs in osteoporosis and osteoarthritis[J]. Bone, 2019, 121: 284-292.

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半乳糖凝集素‑3对骨关节炎成骨细胞矿化的作用研究

The Effect of Galectin‑3 on the Abnormal Mineralization of Osteoarthritic Osteoblasts

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