RESEARCH HIGHLIGHTS Nature Reviews Rheumatology 10, 383 (2014); published online 27 May 2014; doi:10.1038/nrrheum.2014.84
STEM CELLS
Does norepinephrine influence cartilage repair? New work attempting to determine the influence of the sympathetic nervous system in the joint has shown that a major neurotransmitter, norepinephrine, inhibits mesenchymal stem cell (MSC)dependent and cartilage progenitor cell (CPC)-dependent chondrogenesis and, consequently, the regenerative capacity of cartilage. Zsuzsa Jenei-Lanzl et al. first demonstrated the presence of tyrosine hydroxylase (TH)-positive nerve fibres (which can be a local source of norepineprhine) in the synovial tissue, meniscus and bone marrow of patients with knee trauma, and also detected norepinephrine in high concentration in the synovial fluid of these individuals. Neither THpositive cells nor norepinephrine were detected in human
MSC and CPC aggregates at different stages of chondrogenesis; however, these cells did express the adrenergic receptor β2AR, a prerequisite for norepinephrine action. To study the effects of norepinephrine on chondrogenesis, MSCs and CPCs were induced in culture with or without the neurotransmitter for 21 days. Norepinephrine inhibited chondrogenesis in a dose-dependent manner, as demonstrated by morphological changes and decreased production of cartilagespecific type II collagen and sulphated glycosaminoglycans. “This indicates the involvement of β2AR,” explains Jenei-Lanzl, “because norepinephrine in high concentration acts preferentially via β2AR.” Confirming this finding, the specific β2AR agonist isoproterenol inhibited chondrogenesis in vitro. Norepinephrine and isoproterenol also increased expression of type X collagen
NATURE REVIEWS | RHEUMATOLOGY
NPG
and MMP-13, markers of cartilage hypertrophy. Conversely, co-incubation with the specific β2AR antagonist nadolol abrogated this accelerated chondrogenic hypertrophy, and also reversed the inhibitory effects of norepinephrine or isoproterenol on chondrogenesis, in both MSC and CPC cultures. Together, concludes Jenei-Lanzl, the results show that “norepinephrine accelerates hypertrophic chondrogenic differentiation, which is unfavourable for normal cartilage regeneration and might facilitate osteoarthritis development or manifestation after injury”. Sarah Onuora Original article Jenei-Lanzl, Z. et al. Norepinephrine inhibits mesenchymal stem cell and chondrogenic progenitor cell chondrogenesis and accelerates chondrogenic hypertrophy. Arthritis Rheum. doi:10.1002/art.38695
VOLUME 10 | JULY 2014 © 2014 Macmillan Publishers Limited. All rights reserved
STEM CELLS
Does norepinephrine influence cartilage repair? New work attempting to determine the influence of the sympathetic nervous system in the joint has shown that a major neurotransmitter, norepinephrine, inhibits mesenchymal stem cell (MSC)dependent and cartilage progenitor cell (CPC)-dependent chondrogenesis and, consequently, the regenerative capacity of cartilage. Zsuzsa Jenei-Lanzl et al. first demonstrated the presence of tyrosine hydroxylase (TH)-positive nerve fibres (which can be a local source of norepineprhine) in the synovial tissue, meniscus and bone marrow of patients with knee trauma, and also detected norepinephrine in high concentration in the synovial fluid of these individuals. Neither THpositive cells nor norepinephrine were detected in human
MSC and CPC aggregates at different stages of chondrogenesis; however, these cells did express the adrenergic receptor β2AR, a prerequisite for norepinephrine action. To study the effects of norepinephrine on chondrogenesis, MSCs and CPCs were induced in culture with or without the neurotransmitter for 21 days. Norepinephrine inhibited chondrogenesis in a dose-dependent manner, as demonstrated by morphological changes and decreased production of cartilagespecific type II collagen and sulphated glycosaminoglycans. “This indicates the involvement of β2AR,” explains Jenei-Lanzl, “because norepinephrine in high concentration acts preferentially via β2AR.” Confirming this finding, the specific β2AR agonist isoproterenol inhibited chondrogenesis in vitro. Norepinephrine and isoproterenol also increased expression of type X collagen
NATURE REVIEWS | RHEUMATOLOGY
NPG
and MMP-13, markers of cartilage hypertrophy. Conversely, co-incubation with the specific β2AR antagonist nadolol abrogated this accelerated chondrogenic hypertrophy, and also reversed the inhibitory effects of norepinephrine or isoproterenol on chondrogenesis, in both MSC and CPC cultures. Together, concludes Jenei-Lanzl, the results show that “norepinephrine accelerates hypertrophic chondrogenic differentiation, which is unfavourable for normal cartilage regeneration and might facilitate osteoarthritis development or manifestation after injury”. Sarah Onuora Original article Jenei-Lanzl, Z. et al. Norepinephrine inhibits mesenchymal stem cell and chondrogenic progenitor cell chondrogenesis and accelerates chondrogenic hypertrophy. Arthritis Rheum. doi:10.1002/art.38695
VOLUME 10 | JULY 2014 © 2014 Macmillan Publishers Limited. All rights reserved
