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.

骨伸长是由软骨细胞的增殖和生长板中的肥大驱动的。这两个过程均受到包括印度刺猬（IHH）信号传导途径在内的多个信号传导途径的调节。粘多糖贮积酶（MPS）是一组溶酶体贮积病，其特征是糖胺聚糖（GAG）在多个组织和器官中蓄积，导致一系列临床症状，包括通过尚未完全了解的机制引起的骨骼缩短。使用MPS VII小鼠，我们先前观察到了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软骨细胞分泌的IHH在体内和体外均降低。正常软骨细胞对外源性IHH无反应，而MPS VII软骨细胞的增殖在体外对外源性IHH有反应。这伴随着补丁受体（Ptch1）的基因表达升高。这项研究的结果表明，MPS VII生长板中增殖的减少可能部分归因于IHH信号通路的功能障碍。