Recent research on the growth plate: Impact of inflammatory cytokines on longitudinal bone growth.
Children with inflammatory diseases usually display abnormal growth patterns as well as delayed puberty. This is a result of several factors related to the disease itself, such as malnutrition, hypercortisolism, and elevated levels of pro-inflammatory cytokines. These factors in combination with glucocorticoid treatment contribute to growth retardation during chronic inflammation by systemically affecting the major regulator of growth, the GH/IGF1 axis. However, recent studies have also shown evidence of a direct effect of these factors at the growth plate level. In conditions of chronic inflammation, pro-inflammatory cytokines are upregulated and released into the circulation. The most abundant of these, tumor necrosis factor α, interleukin 1β (IL1β), and IL6, are all known to directly act on growth plate cartilage to induce apoptosis and thereby suppress bone growth. Both clinical and experimental studies have shown that growth retardation can partly be rescued when these cytokines are blocked. Therefore, therapy modulating the local actions of these cytokines may be effective for preventing growth failure in patients with chronic inflammatory disorders. In this review, we report the current knowledge of inflammatory cytokines and their role in regulating bone growth.
Pediatric Endocrinology Unit Q2:08Department of Women's and Children's Health, Karolinska University Hospital, SE-171 76 Stockholm, SwedenDevelopmental and Stem Cell BiologyThe Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Bettina
B
Sederquist
Pediatric Endocrinology Unit Q2:08Department of Women's and Children's Health, Karolinska University Hospital, SE-171 76 Stockholm, SwedenDevelopmental and Stem Cell BiologyThe Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Paola
P
Fernandez-Vojvodich
Pediatric Endocrinology Unit Q2:08Department of Women's and Children's Health, Karolinska University Hospital, SE-171 76 Stockholm, SwedenDevelopmental and Stem Cell BiologyThe Hospital for Sick Children, University of Toronto, Toronto, Ontario, CanadaPediatric Endocrinology Unit Q2:08Department of Women's and Children's Health, Karolinska University Hospital, SE-171 76 Stockholm, SwedenDevelopmental and Stem Cell BiologyThe Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Farasat
F
Zaman
Pediatric Endocrinology Unit Q2:08Department of Women's and Children's Health, Karolinska University Hospital, SE-171 76 Stockholm, SwedenDevelopmental and Stem Cell BiologyThe Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada lars.savendahl@ki.se.
Lars
L
Sävendahl
D000293:Adolescent; D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D001848:Bone Diseases, Developmental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002648:Child; D015362:Child Nutrition Disorders / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D005938:Glucocorticoids / Q000009:adverse effects / Q000502:physiology; D006132:Growth Plate / Q000254:growth & development* / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology*
D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators
chondrocyte; cytokines; growth plate; growth retardation; inflammation