Bone elongation is driven by chondrocyte proliferation and hypertrophy in the growth plate. Both processes are modulated by multiple signaling pathways including the Indian Hedgehog (IHH) signaling pathway. Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders characterized by accumulation of glycosaminoglycans (GAGs) in multiple tissues and organs, leading to a range of clinical symptoms including bone shortening through mechanisms that are not fully understood. Using MPS VII mice, we previously observed a reduction in the number of proliferating and hypertrophic chondrocytes and a reduced gene expression of Ihh in the tibial growth plate. We further demonstrate here that IHH secretion by MPS VII chondrocytes was reduced both in vitro and in vivo. While normal chondrocytes showed no response to exogenous IHH, proliferation of MPS VII chondrocytes was stimulated in response to exogenous IHH in vitro. This was accompanied by an elevated gene expression of patched receptor (Ptch1). The results from this study suggested that reduced proliferation in MPS VII growth plate may be partially due to dysfunction of the IHH signaling pathway.

骨伸长是由生长板中的软骨细胞增殖和肥大驱动的。这两个过程均受到多种信号通路的调节，包括 Indian Hedgehog (IHH) 信号通路。粘多糖贮积症 (MPS) 是一组溶酶体贮积症，其特征是糖胺聚糖 (GAG) 在多个组织和器官中积聚，通过尚未完全了解的机制导致一系列临床症状，包括骨缩短。使用 MPS VII 小鼠，我们之前观察到胫骨生长板中增殖和肥大软骨细胞数量的减少以及Ihh基因表达的减少。我们在此进一步证明 MPS VII 软骨细胞的 IHH 分泌在体外和体内均减少。虽然正常软骨细胞对外源性 IHH 没有反应，但在体外， MPS VII 软骨细胞的增殖受到外源性 IHH 的刺激。这伴随着补丁受体（ Ptch1 ）基因表达的升高。这项研究的结果表明，MPS VII 生长板增殖减少可能部分是由于 IHH 信号通路功能障碍所致。