Systemic application of growth hormone enhances the early healing phase of osteochondral defects--a preliminary study in micropigs.
Healing of osteochondral defects following trauma remains a significant clinical problem, often leading to osteoarthritis. Growth hormone (GH) has been shown to accelerate formation of bone and cartilage tissue in the growth plates and in cell cultures. To investigate the influence of systemically administered recombinant porcine growth hormone (r-pGH) on the healing of osteochondral defects we performed a histomorphometrical analysis of full-thickness cartilage defects in the femoral condyle of micropigs. Forty-eight mature female Yucatan micropigs were divided into two groups, one receiving a daily injection of r-pGH (100 microg/kg), the other receiving sodium chloride as placebo. A circular 6-mm-diameter full-thickness defect of the cartilage was created, extending 1.5 mm into the subchondral bone. The animals were sacrificed after 4 (n = 24) and 6 (n = 24) weeks. The von-Kossa stain was used to visualise the calcified structures; cartilage and the fibrous tissue were marked with a combined Safranin-O/light-green stain. The defect filling and the percentage of bone, cartilage, and fibrous tissue into the defect were evaluated using an image analysis system. Furthermore, histological grading was performed using the modified Wakitani score. After 4 weeks no differences were observed between both groups. The defect filling after 6 weeks with newly formed bone was significantly higher in the r-pGH-treated group. The formation of cartilage and fibrous tissue showed a trend towards better healing in the GH-treated group; however, there was no significant difference. In the r-pGH-treated group, the percentage of total defect filling was significantly higher. The evaluation of the vascularity showed a significantly lower number of vessels in the GH-treated group after 6 weeks. Histomorphological grading revealed a significantly lower total Wakitani score in the GH-treated group, which represents a better healing result compared to the controls. The results of the present study suggest that circulating r-pGH or one of its mediators may accelerate osteochondral defect healing by stimulating the formation of osseous and chondral tissue. The analysis of the vascularity leads to the assumption of an advanced maturation of the osteochondral defects under the influence of GH.
Bail
H
H
Department of Trauma and Reconstructive Surgery, Charité, Campus Virchow Clinic, Humboldt University of Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. hermann.bail@charite.de
Klein
P
P
Kolbeck
S
S
Krummrey
G
G
Weiler
A
A
Schmidmaier
G
G
Haas
N P
NP
Raschke
M J
MJ
D000199:Actins / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal; D002146:Bony Callus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D002356:Cartilage / Q000098:blood supply / Q000293:injuries* / Q000502:physiology; D005260:Female; D005269:Femur / Q000098:blood supply / Q000293:injuries* / Q000502:physiology; D013006:Growth Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D013556:Swine, Miniature; D014945:Wound Healing / Q000187:drug effects*
D000199:Actins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone