Canine prostate induces new bone formation in mouse calvaria: A model of osteoinduction by prostate tissue.
BACKGROUND
Osteoblastic metastases are common in patients with advanced prostate cancer. The pathophysiology of the new bone formation at metastatic sites is not currently known, but it is hypothesized that growth factors secreted by the prostate may be involved. Unfortunately, most rodent models of prostate cancer with metastasis to bone are osteolytic and not osteoblastic. Significant osteolysis by tumor cells at metastatic sites may also lead to fractures or bone instability. Misinterpretation of new periosteal bone due to bone instability as tumor-cell osteoinduction is another disadvantage of the osteolytic models. To circumvent these problems, we have developed a model system of new bone formation in the calvaria of nude mice stimulated by normal canine prostate tissue.


METHODS
Collagenase-digested normal prostate tissue was implanted adjacent to the calvaria of nude mice. Calvaria were examined at 2 weeks post-implantation for changes in the bone microenvironment by histology, calcein uptake at sites of bone mineralization, and tartrate-resistant acid phosphatase staining for osteoclasts.


RESULTS
The prostate tissue remained viable and induced abundant new woven bone formation on the adjacent periosteal surface. In some cases new bone formation also was induced on the distant or concave calvarial periosteum. The new bone stained intensely with calcein, which demonstrated mineralization of the bone matrix. The new bone formation on prostate-implanted calvaria significantly increased (1.7-fold) the thickness of the calvaria compared with control calvaria. New bone formation was not induced in calvaria of mice implanted with normal canine kidney, urinary bladder, spleen, or skeletal muscle tissue, or mice with surgically-induced disruption of the periosteum. Osteoclast numbers in the medullary spaces and periosteum of calvaria were mildly increased (61%) in mice with implanted prostate tissue.


CONCLUSIONS
This animal model will be useful for investigating the roles of prostate-derived growth factors on new bone formation in vivo.
LeRoy
Bruce E
BE
Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA.
Bahnson
Robert R
RR
Rosol
Thomas J
TJ
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001859:Bone Neoplasms / Q000503:physiopathology / Q000556:secondary*; D002113:Calcification, Physiologic; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000473:pathology; D004285:Dogs; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010010:Osteoclasts / Q000502:physiology*; D011467:Prostate / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D012886:Skull / Q000166:cytology; D016378:Tissue Transplantation