Göran Anderssons Research Group

Cell- and molecular biology of osteoclasts and bone resorption

Pathological processes leading to the destruction of the skeleton are implicated in several severe and disabilitating processes of importance for public health.

These are inflammatory conditions, such as rheumatoid arthritis; in malignancies either primarily occurring in the skeleton or more commonly as the result of metastatic spread from breast-, prostate or lung-cancer, and in degenerative diseases such as postmenopausal osteoporosis.

The large, multinucleated osteoclast is the cell in the skeleton primarily responsible for resorption of bone. The enzyme tartrate-resistant acid phosphatase (TRAP) is used as a molecular marker for osteoclasts and bone resorption. This enzyme belongs to the family of purple acid phosphatases, containing a di-iron center as an essential component of the active site.

The TRAP/PAP enzyme is secreted from the osteoclast into the resorption area, where the enzyme may modulate osteoclast attachment to bone by dephosphorylation of critical phosphorylated serine residues in the attachment protein osteopontin (OPN). A role for TRAP in the intracellular degradation of phagocytosed material has also recently been established.

Ongoing research in the group includes :

• The structure-function relationships of the TRAP/PAP enzyme using site-directed mutagenesis.
• Mechanisms for activation and secretion of the TRAP/PAP enzyme
• Properties and function of the TRAP/PAP enzyme in the immune and nervous system
• The bone phenotype of TRAP knock-out and transgenic mice
• The functional role of OPN phosphorylation.
• The involvement of TRAP and OPN in cancer metastasis to bone.
• The role of TRAP and OPN in inflammation and arteriosclerosis

Group members

Barbro Ek-Rylander, Senior Researcher

Maria Norgård, technician

Pernilla Lång, Dr MedSc

Serhan Zenger, MSc, graduate student

Christina Patlaka, graduate student

Erik Karlström, graduate student

E-mail

Firstname.Surname@ki.se