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The restricted potential for recovery of growth plate chondrogenesis and longitudinal bone growth following exposure to pro-inflammatory cytokines.
- Source :
-
The Journal of endocrinology [J Endocrinol] 2006 May; Vol. 189 (2), pp. 319-28. - Publication Year :
- 2006
-
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.
- Subjects :
- Animals
Apoptosis physiology
Bone Development drug effects
Cell Count
Cell Division physiology
Cell Line
Chondrocytes physiology
Chondrogenesis drug effects
Chondrogenesis genetics
Gene Expression genetics
Growth Plate drug effects
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
Bone Development physiology
Chondrogenesis physiology
Cytokines pharmacology
Growth Plate physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-0795
- Volume :
- 189
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 16648299
- Full Text :
- https://doi.org/10.1677/joe.1.06609