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Updated: Jun 19, 2026

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Osteoclast migration on phosphorylated osteopontin is regulated by endogenous tartrate-resistant acid phosphatase
Barbro Ek-Rylander1, Göran Andersson
1Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, SE-141 86 Huddinge, Sweden.
Abstract:
Osteopontin (OPN) is a multifunctional protein implicated in cellular adhesion and migration. Phosphorylation has emerged as a post-translational modification important for certain biological activities of OPN. This study demonstrates that adhesion of isolated neonatal rat osteoclasts in vitro was augmented on bovine milk osteopontin (bmOPN) with post-translational modifications (PTMs) compared to human Escherichia-coli-derived recombinant OPN (hrOPN) without PTMs. The difference in adhesiveness between these OPN variants was more pronounced at low coating concentrations (= 10 mug/ml). Both OPN forms adhered exclusively using a beta(3)-integrin. Partial (=50%) dephosphorylation by tartrate-resistant acid phosphatase (TRAP) in vitro reduced osteoclast attachment to bmOPN to the same level as to hrOPN, demonstrating the importance of specific phosphorylations in OPN-dependent osteoclast adhesion. The involvement of PTMs of OPN in migration of primary rat and mouse osteoclasts was assessed on culture dishes coated with the different OPN forms and then overlaid with gold particles. Here, osteoclasts exhibited haptotactic migration on bmOPN but did not migrate on hrOPN. The presence of neutralizing antibodies to TRAP inhibited migration on bmOPN. Moreover, migration of osteoclasts isolated from TRAP-overexpressing transgenic mice was augmented on bmOPN, but not on hrOPN or type I collagen. These data collectively provide evidence in favor of a role for endogenous TRAP in regulating osteoclast migration on post-translationally modified OPN. In a tissue context, modulation of the phosphorylation level of OPN by extracellular phosphatases, e.g., TRAP, could regulate the extent of degradation such as depth and area at each bone resorption site by triggering osteoclast detachment and facilitate subsequent migration on the bone surface.
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