[HTML][HTML] Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice

W Zhao, MH Byrne, BF Boyce… - The Journal of clinical …, 1999 - Am Soc Clin Investig
W Zhao, MH Byrne, BF Boyce, SM Krane
The Journal of clinical investigation, 1999Am Soc Clin Investig
Parathyroid hormone (PTH) stimulates bone resorption by acting directly on
osteoblasts/stromal cells and then indirectly to increase differentiation and function of
osteoclasts. PTH acting on osteoblasts/stromal cells increases collagenase gene
transcription and synthesis. To assess the role of collagenase in the bone resorptive actions
of PTH, we used mice homozygous (r/r) for a targeted mutation (r) in Col1a1 that are
resistant to collagenase cleavage of type I collagen. Human PTH (1–34) was injected …
Parathyroid hormone (PTH) stimulates bone resorption by acting directly on osteoblasts/stromal cells and then indirectly to increase differentiation and function of osteoclasts. PTH acting on osteoblasts/stromal cells increases collagenase gene transcription and synthesis. To assess the role of collagenase in the bone resorptive actions of PTH, we used mice homozygous (r/r) for a targeted mutation (r) in Col1a1 that are resistant to collagenase cleavage of type I collagen. Human PTH(1–34) was injected subcutaneously over the hemicalvariae in wild-type (+/+) or r/r mice four times daily for three days. Osteoclast numbers, the size of the bone marrow spaces and periosteal proliferation were increased in calvariae from PTH-treated +/+ mice, whereas in r/r mice, PTH-induced bone resorption responses were minimal. The r/r mice were not resistant to other skeletal effects of PTH because abundant interstitial collagenase mRNA was detected in the calvarial periosteum of PTH-treated, but not vehicle-treated, r/r and +/+ mice. Calcemic responses, 0.5–10 hours after intraperitoneal injection of PTH, were blunted in r/r mice versus +/+ mice. Thus, collagenase cleavage of type I collagen is necessary for PTH induction of osteoclastic bone resorption.
The Journal of Clinical Investigation