Regeneration of injured articular cartilage using the recombinant human amelogenin protein.

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Bone & Joint Research Pub Date : 2023-10-03 DOI:10.1302/2046-3758.1210.BJR-2023-0019.R1
Omer Helwa-Shalom, Faris Saba, Elad Spitzer, Salem Hanhan, Koby Goren, Shany I Markowitz, Dekel Shilo, Nissim Khaimov, Yechiel N Gellman, Dan Deutsch, Anat Blumenfeld, Hani Nevo, Amir Haze
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Abstract

Aims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.

Methods: A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM+ using immunohistochemistry and immunofluorescence.

Results: A total of 12 weeks after treatment, 0.5 μg/μl rHAM+ brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment.

Conclusion: We found that 0.5 μg/μl rHAM+ induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment.

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用重组人釉原蛋白修复关节软骨损伤。
目的:软骨损伤很少自发愈合,通常需要手术干预,导致生物力学下纤维组织的形成。本研究旨在评估釉原蛋白对大鼠大鼠骨软骨损伤(OCI)愈合过程的可能影响。方法:在93只大鼠的右腿股骨滑车上建立可重复的大OCI。用0.1、0.5、1.0、2.5或5.0μg/μl溶于丙二醇藻酸盐(PGA)载体的重组人釉原蛋白(rHAM+)或单独用PGA载体处理OCI。治疗12周后,通过形态计量学分析和组织学评估评估愈合程度。在用0.5μg/μl rHAM+处理后4天,使用免疫组织化学和免疫荧光评估损伤部位的细胞募集以及迁移细胞的起源。结果:治疗12周后,0.5μg/μl rHAM+可显著修复软骨下骨和软骨。在缺损表面显示蛋白多糖和II型胶原表达增加,I型胶原表达减少,在新形成的潮痕区域显示X型胶原水平升高。相反,对照组表现出骨关节炎的改变。治疗四天后,观察到表达间充质干细胞(MSC)标志物CD105和STRO-1的细胞从邻近骨髓向OCI募集。结论:我们发现,0.5μg/μl rHAM+在大鼠模型中诱导了损伤的关节软骨和软骨下骨的体内愈合,通过治疗后几天的旁分泌细胞募集,预防了对照OCI中出现的破坏性创伤后骨关节炎变化。
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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