Identification of functional insulin‐like growth factor‐II/mannose‐6‐phosphate receptors in isolated bone cells

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Abstract
The role of the IGF-II/cation independent mannose-6-phosphate (IGF-II/M6P) receptor in the transduction of cellular effects evoked by IGF-II has been extensively debated in the literature. Many reports suggest that IGF-II transduces its effects through the IGF-I receptor, while others show that IGF-II utilizes the type II receptor to affect cellular activity. This study (1) verifies the presence of the IGF-II/M6P receptor in rat calvarial osteoblasts, and (2) evaluates the ability of the receptor to initiate intracellular single. Using conventional receptor binding assays, it was found that osteoblasts bind IGF-II with high affinity. Scatchard analyses indicated that there are 5.08 × 104 IGF-II/M6P receptor per osteoblast with a Kd near (2.0 nM). The receptor protein was further identified by cross-linking with 125I-IGF-II. Northern analysis was used to identify an mRNA transcript for the IGF-II/M6P receptor protein. To examine if the IGF-II/M6P receptor can initiate second messenger signals, the ability of IGF-II to evoke Ca2+ transients was evaluated. Osteoblasts pretreated with IGF-I did not lose their ability to respond to IGF-II. Further, a polyclonal antibody against the rat IGF-II/M6P receptor (R-II-PAB1) (1) was able to evoke its own Ca2+ response, and (2) was able to block the generation of Ca2+ transients caused by IGF-II. The data in this report show that the osteoblastic Ca2+ response to IGF-II appears to be caused by an intracellular release of Ca2+ which is mediated by the IGF-II/M6P receptor making it possible to envision how the receptor may be an important modulator of osteoblast mediated osteogenesis.

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