Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Control of anabolic effect of Parathyroid Hormone by chemokine MCP1 in the osteoblast/osteocyte lineage. (#327)

Nigel Morrison 1 , Mitchel Jones 1 , Susan Millard 2 , Allison Pettit 2 , Mark Forwood 1
  1. School of Pharmacy and Medical Science, Griffith University, Gold Coast, Queensland, Australia
  2. Bones and Immunology Group, Mater Research Institute-UQ, Brisbane, QLD, Australia

The anabolic effect of Parathyroid Hormone (PTH 1-34, also known as Teriparatide) provides a potent anti-osteoporosis treatment, marketed as Forteo. In rat bone, the chemokine MCP1 (also known as CCL2) is induced about 250-fold occurring within 1 hour of PTH injection and is the highest induced gene. In mice, we previously showed that global knockout (KO) of MCP1 blocked the anabolic effect of PTH. In the present work, we used cre-lox genetic models to generate cell lineage specific MCP1 KO in the osteoblast/osteocyte lineage by using the type 1 collagen promoter (Col1A1) to drive cre recombinase in mice carrying lox sites flanking the MCP1 gene (MCP1ff). In contrast to a 3.6 standard deviation (SD) increase in total bone in the proximal tibial metaphysis (p=4x10-9) in control mice, there was no response to anabolic PTH in mice in which the MCP1 gene was deleted (MCP1ff Col-cre+, p=0.6). We then tested whether ovariectomy (OVX) induced bone loss could be suppressed by simultaneous anabolic PTH treatment (OVX-PTH) in such animals. In control animals, OVX resulted in a 2.0SD decrease in bone density. OVX-PTH treated animals had bone density 1.6SD higher than baseline untreated and 2.6SD increased from the low OVX level. In contrast, the anabolic PTH effect was significantly blunted (p=0.01) in OVX MCP1ff Col-cre+ animals with a reduced 1.4SD change. These data suggests a role for osteoblast/osteocyte expressed MCP1 in the anabolic effect of PTH.