| Autor: |
Deosthale, Padmini, Hong, Jung Min, Essex, Alyson L., Rodriguez, Wilyaret, Tariq, Dua, Sidhu, Harmandeep, Marcial, Alejandro, Bruzzaniti, Angela, Plotkin, Lilian I. |
| Zdroj: |
Bone Reports; June 2022, Vol. 16 Issue: 1 |
| Abstrakt: |
Pannexin1 (Panx1) is a hemichannel-forming protein that participates in the communication of cells with the extracellular space. To characterize the role of osteoclastic Panx1 on bone, Panx1fl/fl;TRAP-Cre (Panx1ΔOc) mice were generated, and compared to Panx1fl/fllittermates at 6 weeks of age. Total and femoral BMD was ~20% lower in females and males whereas spinal BMD was lower only in female Panx1ΔOcmice. μCT analyses showed that cortical bone of the femoral mid-diaphysis was not altered in Panx1ΔOcmice. In contrast, cancellous bone in the distal femur and lumbar vertebra was significantly decreased in both female and male Panx1ΔOcmice compared to Panx1fl/flcontrols and was associated with higher osteoclast activity in female Panx1ΔOcmice, with no changes in the males. On the other hand, vertebral bone formation was decreased for both sexes, resulting from lower mineral apposition rate in the females and lower mineralizing surface in the males. Consistent with an osteoclastic effect in female Panx1ΔOcmice, osteoclast differentiation with RANKL/M-CSF and osteoclast bone resorbing activity in vitrowere higher in female, but not male, Panx1ΔOcmice, compared to Panx1fl/fllittermates. Surprisingly, although Panx1 expression was normal in bone marrow stromal-derived osteoblasts from male and female Panx1ΔOcmice, mineral deposition by male (but not female) Panx1ΔOcosteoblasts was lower than controls, and it was reduced in male Panx1fl/flosteoblasts when conditioned media prepared from male Panx1ΔOcosteoclast cultures was added to the cell culture media. Thus, deletion of Panx1 in TRAP-expressing cells in female mice leads to low bone mass primarily through a cell autonomous effect in osteoclast activity. In contrast, our evidence suggests that changes in the osteoclast secretome drive reduced osteoblast function in male Panx1ΔOcmice, resulting in low bone mass. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
