RRC ID 42631
Author MacRae VE, Farquharson C, Ahmed SF.
Title The restricted potential for recovery of growth plate chondrogenesis and longitudinal bone growth following exposure to pro-inflammatory cytokines.
Journal J Endocrinol
Abstract Childhood chronic inflammatory disease can be associated with transient and permanent growth retardation. This study examined the potential for spontaneous growth recovery following pro-inflammatory cytokine exposure. Murine ATDC5 chondrogenic cells and postnatal metatarsals were exposed to interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNFalpha), and their growth and proliferative capacity were determined following recovery. TNFalpha and IL-1beta reduced chondrocyte proliferation and aggrecan and collagen types II and X expression at minimum concentrations of 10 ng/ml and 0.1 ng/ml respectively. TNFalpha but not IL-1beta exposure led to increased caspase-3 activity and altered cellular morphology, consistent with reduced viability. Cytokine exposure particularly inhibited proteoglycan synthesis. This effect was dose and duration dependent. Compared with the control, IL-1beta and TNFalpha led to a 71% and 45% reduction in metatarsal growth after 8 days of exposure respectively (P < 0.05). An additive effect of IL-1beta combined with TNFalpha was observed (110% decrease; P < 0.05). Metatarsals exposed to IL-1beta or TNFalpha individually for a 2-day period, and allowed to recover spontaneously in the absence of cytokines for a further 6 days, showed normal growth trajectories. In combination, growth was 59% lower (P < 0.01) compared with control metatarsals at the end of the recovery period. Exposure to the combination for 4 days followed by a 4-day recovery period resulted in 87% decrement compared with controls (P < 0.05). IL-6 did not alter any parameter studied. IL-1beta and TNFalpha exert diverse inhibitory effects on ATDC5 chondrocyte dynamics and metatarsal growth. The extent of recovery following cytokine exposure depends on the duration of exposure, and may be incomplete following longer periods of exposure.
Volume 189(2)
Pages 319-28
Published 2006-5-1
DOI 10.1677/joe.1.06609
PII 189/2/319
PMID 16648299
MeSH Animals Apoptosis / physiology Bone Development / drug effects Bone Development / physiology* Cell Count Cell Division / physiology Cell Line Chondrocytes / physiology Chondrogenesis / drug effects Chondrogenesis / genetics Chondrogenesis / physiology* Cytokines / pharmacology* Gene Expression / genetics Growth Plate / drug effects Growth Plate / physiology* Interleukin-1 / pharmacology Interleukin-6 / pharmacology Metatarsal Bones / drug effects Metatarsal Bones / growth & development Mice Organ Culture Techniques Organ Size Proteoglycans / biosynthesis Tumor Necrosis Factor-alpha / pharmacology
IF 4.041
Times Cited 79
Human and Animal Cells