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December 9-10, 2019 | Barcelona, Spain
Volume 14
ARTHRITIS AND RHEUMATOLOGY
ANATOMY AND PHYSIOLOGY
13
th
International Conference on
3
rd
International Conference on
&
Journal of Orthopaedics Trauma Surgery
and Related Research
Rheumatology Congress 2019 & Anatomy and Physiology 2019
December 09-10, 2019
J Orthop Trauma Surg Rel Res, ISSN: 1897-2276
Humanin treatment, a potential new strategy to prevent bone growth impairment in
chronic inflammatory disorders
Yunhan Zhao
Karolinska University, Sweden
Statement of the Problem
: Children with chronic inflammatory conditions such as inflammatory bowel disease (IBD) often
suffer from bone growth impairment which has been linked to increased levels of pro-inflammatory cytokines, including IL-
1β and TNF-α, and treatment with high doses of glucocorticoids. Humanin is an endogenous anti-apoptotic protein which in
preclinical studies has been shown to prevent glucocorticoid-induced bone growth impairment, without interfering with the
desired anti-inflammatory effects of glucocorticoids. We hypothesized that systemic levels of humanin are decreased in growth
retarded children with inflammatory bowel disease (IBD) and that treatment with a humanin analogue (HNG) can prevent
cytokine-induced bone growth impairment.
Methodology & Theoretical Orientation
: Humanin levels were measured by ELISA in serum samples obtained from 40 short
children with IBD and in gender-matched healthy controls. Ex vivo cultured fetal rat metatarsal bones were treated with the
pro-inflammatory cytokines IL-1β plus TNF-α (10 ng/ml each) and/or HNG (300 ng/ml) while bone growth was followed for
12 days.
Findings
: Serum humanin levels were significantly decreased in the IBD patients
when compared to healthy controls (p < 0.01). The cytokines TNF-α and IL1-β acted in
synergy to suppress metatarsal bone growth (p < 0.001 vs control) and this effect could
be partly prevented when co-cultured with HNG (p < 0.01 vs cytokines only).
Conclusion & Significance
: Our data suggests that systemic levels of humanin
are decreased in patients with chronic inflammation who suffer from bone growth
impairment. Interestingly, the human analogue HNG was found to partially prevent
cytokine-induced growth impairment in ex vivo cultured rat metatarsal bones. Our
findings suggest that humanin is a potential drug target for the prevention of bone growth
impairment in conditions of chronic inflammation.
Biography
Yunhan Zhao is a PhD student from Karolinska Institutet. His project is on Prevention of growth failure and osteoporosis in chronic
inflammation. The aims of his studies are to explore the molecular mechanisms of GC-induced growth failure and osteoporosis,
and to investigate the potential for humanin analogues, in combination with GCs to prevent osteoporosis and bone growth failure in
inflammatory diseases.
yunhan.zhao.1@ki.se