Department of Paediatric Orthopaedics, Christian Medical College, Vellore, India; Division of Paediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden; Centre for Stem Cell Research, a Unit of InStem Bengaluru, Christian Medical College, Bagayam, Vellore, India.
Division of Paediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.
Bone. 2022 Jan;154:116186. doi: 10.1016/j.bone.2021.116186. Epub 2021 Sep 11.
The process of longitudinal bone growth occurs at the growth plate where the chondrocytes undergo apparent structural and molecular changes to promote growth. Recent reports suggest that radial shockwave treatment (rSWT) stimulates bone length in cultured fetal rat metatarsals. Therefore, we investigated if rSWT has similar growth promoting effects on cultured human growth plate fragments and addressed the same in a preclinical in vivo rabbit model by subjecting their growth plates to rSWT.
Short-term effects of high-energy rSWT were evaluated in a unique model of cultured human growth plate cartilage (n = 5) wherein samples exposed to rSWT were assessed for chondrogenic markers at 24 h in comparison to unexposed samples obtained from the same limb. Local in vivo effects were studied in six-week-old rabbits who had their distal femurs exposed to four weekly sessions of rSWT at low- and high-energy levels (n = 4 each). At sacrifice, histomorphometric and immunohistochemistry analyses were performed. For effect on longitudinal growth, proximal tibiae of 22-week-old rabbits (n = 12) were asymmetrically exposed to rSWT; the contralateral side served as untreated controls. At sacrifice, the final bone length was measured.
In the ex vivo model of cultured human growth plate cartilage, rSWT exposure upregulated SOX9 and COL2A1 compared to control. In the immature rabbit model, an increased number of proliferative chondrocytes and column density was seen for both the energy levels. In the adolescent rabbits, an increase in tibial length was observed after the fourth session of high-energy rSWT and until six-weeks after rSWT compared to the untreated limb.
Our preliminary experimental results suggest that rSWT may serve as a non-invasive treatment and possibly a safe strategy to stimulate longitudinal bone growth. However, further studies are needed to assess the in vivo effects of rSWT in models of disturbed bone growth.
纵向骨生长发生在生长板，软骨细胞在那里经历明显的结构和分子变化以促进生长。最近的报告表明，径向冲击波治疗（rSWT）刺激培养的胎鼠跖骨的骨长度。因此，我们研究了 rSWT 是否对培养的人生长板碎片具有类似的促进生长作用，并通过将其生长板暴露于 rSWT 来在临床前兔模型中解决相同的问题。
在培养的人生长板软骨的独特模型中评估高能量 rSWT 的短期影响（n=5），其中暴露于 rSWT 的样本在 24 小时与从同一肢体获得的未暴露样本相比评估软骨形成标志物。在 6 周龄的兔子中研究局部体内效应，这些兔子的股骨远端接受低能量和高能量水平的 rSWT 每周 4 次（每组各 4 只）。处死时进行组织形态计量学和免疫组织化学分析。为了研究对纵向生长的影响，将 22 周龄的兔子（n=12）的胫骨近端不对称地暴露于 rSWT；对侧作为未处理的对照。处死时测量最终骨长。
在培养的人生长板软骨的离体模型中，rSWT 暴露与对照组相比上调了 SOX9 和 COL2A1。在未成熟的兔模型中，两种能量水平均可见增殖软骨细胞和柱密度增加。在青少年兔子中，与未处理的肢体相比，在高能量 rSWT 的第四次治疗后直至 rSWT 后 6 周，胫骨长度增加。
我们的初步实验结果表明，rSWT 可能作为一种非侵入性治疗方法，并且可能是刺激纵向骨生长的安全策略。然而，需要进一步的研究来评估 rSWT 在骨生长障碍模型中的体内效应。
