Treatment with insulin-like growth factor-1 increases chondrogenesis by periosteum in vitro.
The repair of defects in articular cartilage with hyaline tissue that is resilient to wear is a challenging problem. Fibrocartilaginous tissue forms in response to injury through the articular surface and degenerates under mechanical load. Because periosteum contains cells, which are capable of synthesizing cartilage matrix proteins, it has been used to repair defects in articular surfaces. Treatment of periosteal grafts with growth factors, particularly those that elicit chondrocyte gene expression, may improve tissue regeneration. Gene expression by periosteal explants in vitro was measured. Expression of type II collagen and aggrecan mRNA was increased in response to treatment with IGF-I. Furthermore, IGF-I treatment caused an increase in type II collagen and aggrecan mRNA that was time and concentration dependent. The effect of short and long-term (continuous) incubations was compared to determine if a pretreatment could be used to condition a graft for subsequent surgical use. Short-term incubation in vitro with IGF-I followed by incubation without IGF-I was nearly as effective at increasing expression of type II collagen and aggrecan mRNA as incubation for the same length of time with IGF-I present continuously in the culture media. Treatment with IGF-I also produced cell clustering and nodule formation which are indicative of chondrogenesis. These results suggest that pretreatment with IGF-I in vitro may enhance the effectiveness of a graft to produce hyaline cartilage in vivo. Whether the cellular and molecular changes we have observed can lead to the formation of tissue that withstands the mechanical forces exerted by weight bearing remains to be determined.
Mierisch
C M
CM
Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Virginia, School of Medicine, Charlottesville, VA 22908, USA.
Anderson
P C
PC
Balian
G
G
Diduch
D R
DR
D053674:Aggrecans; D000818:Animals; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins; D015870:Gene Expression / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D037181:Lectins, C-Type; D008297:Male; D010521:Periosteum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
D053674:Aggrecans; D024043:Collagen Type II; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I