Protective effect of parathyroid hormone (1-34) against early osteoarthritis in mice with type 1 diabetes mellitus

Lei YANG; Sixu CHEN; Daocheng LIU; Quanwei BAO; Jiazhi YANG; Sihao HE; Huayu LIU; Zhaowen ZONG

doi:10.16016/j.1000-5404.201805136

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Protective effect of parathyroid hormone (1-34) against early osteoarthritis in mice with type 1 diabetes mellitus

Basic Medicine | 更新时间：2026-01-09

- Protective effect of parathyroid hormone (1-34) against early osteoarthritis in mice with type 1 diabetes mellitus
- Journal of Third Military Medical University Vol. 40, Issue 22, Pages: 2034-2039(2018)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)陆军卫勤训练基地战救技能训练教研室
  2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院急诊科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201805136
  CLC： R587.1;R684.3;R977.14
- Received：18 May 2018，
  
  Revised：2018-06-17，
  
  Published：30 November 2018
- 稿件说明：
移动端阅览
Lei YANG, Sixu CHEN, Daocheng LIU, et al. Protective effect of parathyroid hormone (1-34) against early osteoarthritis in mice with type 1 diabetes mellitus[J]. Journal of Third Military Medical University, 2018, 40(22): 2034-2039.
DOI：

Lei YANG, Sixu CHEN, Daocheng LIU, et al. Protective effect of parathyroid hormone (1-34) against early osteoarthritis in mice with type 1 diabetes mellitus[J]. Journal of Third Military Medical University, 2018, 40(22): 2034-2039. DOI： 10.16016/j.1000-5404.201805136.

摘要

目的

观察重组人甲状旁腺素(parathyroid hormone

PTH1-34)对1型糖尿病(type 1 diabetes mellitus

T1DM)小鼠手术诱导的关节炎模型早期骨关节炎(osteoarthritis，OA)的影响。

方法

分别取12周龄的C57BL/6J雄性小鼠，采用完全随机分组法分为野生小鼠组(WT组)、T1DM小鼠组(T1DM组)和T1DM小鼠PTH1-34干预组(T1DM+PTH组)，利用链脲佐菌素(streptozotocin，STZ；45 mg/kg)腹腔注射建立T1DM小鼠模型，3组右下肢内侧半月板切除手术诱导OA小鼠模型；以野生小鼠未建模的左下肢作为对照组。标本获得后分别采用CT扫描重建、HE染色、番红O-固绿染色、OA软骨组织病理学评分观察小鼠膝关节软骨下骨骨量的变化及OA样改变，并进行统计学分析。

结果

CT扫描分析显示WT组OA关节软骨下骨骨体积占组织总体积百分比(BV/TV)较对照组关节下降(0.329

0.351，

0.05)，软骨下骨骨小梁数量(Tb.N)及厚度(Tb.Th)分别下降9.9%和8.2%(

0.05)；T1DM组OA关节软骨下骨BV/TV较WT组OA关节下降明显(0.241

0.329，

0.05)，软骨下骨Tb.N及Tb.Th分别下降20.2%和11.2%(

0.05)；T1DM+PTH组OA关节较T1DM组OA关节软骨下骨BV/TV改善明显(0.301

0.241，

0.05)，软骨下骨Tb.N及Tb.Th分别上升14.9%和9.9%(

0.05)。组织病理学评分显示建模组均形成OA样改变，评分结果提示：T1DM组OA关节关节炎评分明显高于WT组OA关节(

0.05)；应用PTH1-34干预，T1DM+PTH组小鼠OA关节关节炎评分低于T1DM组OA关节(

0.05)。

结论

OA早期伴有软骨下骨骨量降低，T1DM可加速骨量的丢失并促进OA早期进展，使用PTH1-34后可逆转T1DM小鼠OA早期软骨下骨骨量丢失，在T1DM OA发生早期起到保护作用。

Abstract

Objective

To investigate the protective effect of exogenous parathyroid hormone (PTH1-34) against early osteoarthritis induced by surgery in a mouse model of type 1 diabetes mellitus (T1DM).

Methods

Twelve-week-old male C57BL/6J mice were randomly divided into control group (Con group) wild-type group (WT group)

type 1 diabetes group (T1DM group) and type 1 diabetes with PTH1-34 intervention group (T1DM+PTH group). A mouse model of T1DM was established by intraperitoneal injection of streptozotocin (STZ

45 mg/kg)

and osteoarthritis (OA) was induced by medial meniscectomy; for PTH1-34 intervention

the mice received daily intraperitoneal injection of 10 μL/g of 0.001% PTH1-34 for 3 consecutive weeks. CT scan reconstruction

HE staining

safranin O-fast green staining

osteoarthritis cartilage histopathology scores were used to assess the changes of subchondral bone volume and osteoarthritis-like changes in the knee joints of the mice.

Results

In WT group

CT scan showed a significantly lowered percentage of subchondral bone volume in the total tissue volume (BV/TV) in the knee with surgically induced OA compared with the con group (0.329

0.351

0.05)

and the number and thickness of the trabecular bone (Tb.N and Tb.Th

respectively) in the subchondral bone were decreased by 9.9% and 8.2% in the knee with OA

respectively (

0.05). In T1DM group

BV/TV of the subchondral bone in the knee with OA was significantly lower than that in WT group (0.241

0.329

0.05)

and Tb.N and Tb.Th in the subchondral bone were decreased by 20.2% and 11.2%

respectively (

0.05). PTH1-34 treatment significantly improved the BV/TV in the diabetic mice (0.301

0.241

0.05) and increased subchondral bone Tb.N and Tb.Th by 14.9% and 9.9%

respectively (

0.05). Assessment based on the arthritis scores showed the occurrence of osteoarthritis-like changes in all the 3 groups; the score was significantly higher in T1DM group than in WT group (

0.05)

and was significantly lower

in T1DM+PTH group than in T1DM group (

0.05).

Conclusion

Early-stage OA is associated with subchondral bone loss

and type 1 diabetes can accelerate the bone loss and exacerbate early progression of OA. PTH1-34 treatment can reverse subchondral bone loss and thus offers protection in diabetic mice with early OA.

关键词

Keywords

references

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