Indian Hedgehog (Ihh), a member of the Hh family, is a crucial paracrine factor involved in vertebrate development and homeostasis. It participates in the Hedgehog (Hh) signaling pathway, along with cell surface receptor Ptch1, Smo, and Gli transcription factors. Ihh has significant roles in processes like chondrocyte proliferation, differentiation, and bone formation, influencing the development of various craniofacial structures, joints, and bones [1]. The generation of genetic models, such as the Ihh-mKate2-Dre knock-in mouse line, has been valuable for studying the function of Ihh-expressing cells and their progeny [3].

In Ihh-null mice, symphyseal development is defective due to enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells, indicating Ihh's essential role in symphyseal cartilage development and anterior mandibular growth [6]. In Sp7-iCre; Ihhfl/fl mice, where Ihh is specifically deleted in Sp7-expressing cells, a dwarfism phenotype with severe skeletal dysplasia and lethality at birth occurs, showing Ihh's role in osteoblast differentiation, mineralization, and embryonic osteogenesis [5]. In MPS VII mice, reduced Ihh secretion leads to a decrease in chondrocyte proliferation in the growth plate [4]. Conditional Ihh knockout in mouse chondrocytes down-regulates Hif-2α protein expression in early degenerative cartilage tissue, affecting the expression of downstream factors and exacerbating cartilage degeneration during osteoarthritis progression [2].

In conclusion, Ihh is essential for multiple developmental and homeostatic processes, especially those related to chondrocyte and osteoblast function, craniofacial development, and joint health. Gene-knockout mouse models, like Ihh-null, Sp7-iCre; Ihhfl/fl, and conditional Ihh knockout in chondrocytes, have been instrumental in revealing Ihh's functions in these processes, providing insights into potential therapeutic strategies for diseases such as osteoarthritis and skeletal dysplasias.