ijmm_36_2_571_PDFCysteine induces longitudinal bone growth in mice by upregulating IGF-I.

“Cysteine (Cys) is known to exert various effects, such as antioxidant, antipancreatitic and antidiabetic effects. However, the effects of Cys on longitudinal bone growth have not been elucidate to date. Thus, the aim of the present study was to evaluate the effects of Cys on bone growth. Growth‑plate thickness and bone parameters, such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connectivity density (Conn.D) and total porosity were analyzed by means of micro-computed tomography (µCT). The levels of serum insulin‑like growth factor‑I (IGF‑I) were measured by enzyme‑linked immunosorbent assay (ELISA). Hepatic IGF‑I mRNA expression was analyzed by quantitative polymerase chain reaction (qPCR). The phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) was investigated by western blot analysis. Our results revealed that Cys increased IGF‑I mRNA expression in HepG2 cells. The thickness of the growth plates was increased following treatment with Cys. Moreover, BV/TV, Tb.Th, TbN, Conn.D and total porosity were improved following treatment with Cys. Hepatic IGF‑I mRNA expression and serum IGF‑I levels were increased by Cys. The levels of phosphorylated JAK2 and STAT5 were elevated by Cys. The findings of our study indicate that Cys increases the thickness of growth plates through the upregulation of IGF‑I, which results from the phosphorylation of JAK2-STAT5. Thus, our data suggest that Cys may have potential for use as a growth-promoting agent.”

Cysteine is found in dietary sources but it may be possible to be deficient.

“Treatment with 50 mg/ml of Cys had the most prominent effect, and thus we evaluated the effects of treatment with 50 mg/kg of Cys in the next set of experiments, i.e., in vivo mouse models.”

“The thickness of the growth plates in the proximal tibias in the CON and PEM{protein deficient group} groups were 124.0±2.9 and 90.1±3.1, respectively; the growth-plate thickness in the Cys group was 117.0±4.3″<-Cysteine did not increase growth plate thickness versus control group.

“the levels of p-JAK2 and p-STAT5 in the liver were decreased due to malnutrition. However, the decrease in the levels of p-JAK2 and p-STAT5 was reversed by treatment with Cys”

“In general, endochondral cell proliferation in the growth plate results in bone growth. Thus, growth-plate thickness is a direct indicator of linear bone growth”