BACKGROUND INFORMATION: Sema-7A is a glycosylphosphatidylinositol-anchored semaphorin that was first identified in the immune system. It is a member of a large family of proteins involved in axon guidance signalling. Sema-7A is expressed in the myeloid and the lymphoid lineage and seems to be involved in cytokine expression and chemotaxy through its receptor Plexin C1. However, it can promote axon outgrowth, acting through a beta1 subunit-containing integrin receptor. RESULTS AND CONCLUSIONS: In the present study, we have investigated its regulation and function in bone cells. Semiquantitative reverse transcriptase-PCR demonstrated that Sema-7A mRNA is present during all stages of osteoblast differentiation and maturation in mouse calvaria cells and in MC3T3 cell line in vitro. Its expression is also regulated during primary osteoclast differentiation in vitro. We report that Sema-7A is capable of increasing the migration of MC3T3 cells and that this process is mediated by the mitogen-activated protein kinase pathway in osteoblasts, probably through the integrin subunit beta1. Moreover, the addition of recombinant soluble Sema-7A to the culture enhances osteoclast fusion. These findings indicate for the first time the possible involvement of Sema-7A in bone cell differentiation.
BACKGROUND INFORMATION: Sema-7A is a glycosylphosphatidylinositol-anchored semaphorin that was first identified in the immune system. It is a member of a large family of proteins involved in axon guidance signalling. Sema-7A is expressed in the myeloid and the lymphoid lineage and seems to be involved in cytokine expression and chemotaxy through its receptor Plexin C1. However, it can promote axon outgrowth, acting through a beta1 subunit-containing integrin receptor. RESULTS AND CONCLUSIONS: In the present study, we have investigated its regulation and function in bone cells. Semiquantitative reverse transcriptase-PCR demonstrated that Sema-7A mRNA is present during all stages of osteoblast differentiation and maturation in mouse calvaria cells and in MC3T3 cell line in vitro. Its expression is also regulated during primary osteoclast differentiation in vitro. We report that Sema-7A is capable of increasing the migration of MC3T3 cells and that this process is mediated by the mitogen-activated protein kinase pathway in osteoblasts, probably through the integrin subunit beta1. Moreover, the addition of recombinant soluble Sema-7A to the culture enhances osteoclast fusion. These findings indicate for the first time the possible involvement of Sema-7A in bone cell differentiation.
Authors: Larry Pederson; Ming Ruan; Jennifer J Westendorf; Sundeep Khosla; Merry Jo Oursler Journal: Proc Natl Acad Sci U S A Date: 2008-12-15 Impact factor: 11.205