Histologic and dynamic changes induced by chronic metabolic acidosis in the rat growth plate.
To understand better the pathophysiology of growth impairment in persistent metabolic acidosis, the morphology and dynamics of the growth plate were studied in young rats grouped as follows: rats that were made acidotic by oral administration of ammonium chloride for 14 d (AC), nonacidotic rats that were fed ad libitum (control [C]), and nonacidotic rats that were pair-fed with the AC group (PF). AC rats became markedly acidotic and growth retarded. The volume of newly formed bone per day (mean +/- SEM) was significantly lowered (P < 0.05) in AC rats (AC, 3.4 +/- 0.4; C, 8.4 +/- 0.6; PF, 6.4 +/- 0.5 mm(3)/d). Growth plate height was lower in AC rats (303.8 +/- 12.7 microm) than in either C (478.0 +/- 16.0 microm) or PF rats (439.0 +/- 21.4 microm). The processes of chondrocyte proliferation (assessed by bromodeoxyuridine labeling) and maturation (assessed by stereologic estimators of size and shape of chondrocytes and the volume of matrix per cell) were not impaired by acidosis. By contrast, the dynamics of hypertrophic chondrocytes were altered significantly: both cell turnover per column per day (AC, 4.4 +/- 0.4; C, 8.0 +/- 0.8; PF, 6.2 +/- 0.6) and linear velocity of advance of chondrocytes (AC, 5.7 +/- 0.5; C, 11.2 +/- 0.9; PF, 9.4 +/- 0.8 microm/h) were lowered significantly. The study presented here shows the inhibitory effect of metabolic acidosis on cartilage cell progression and endochondral bone formation. Finally, the data show that metabolic acidosis caused a marked shortening of the growth plate because chondrocyte turnover was affected to a greater extent than bone tissue formation.
Carbajo
Eduardo
E
Department of Anatomy, School of Medicine, Hospital Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
López
José Manuel
JM
Department of Cell Biology, School of Medicine, Hospital Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
Santos
Fernando
F
Department of Pediatrics, IUOPA, School of Medicine, Hospital Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
Ordóñez
Flor Angel
FA
Department of Pediatrics, IUOPA, School of Medicine, Hospital Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
Niño
Pilar
P
Department of Anatomy, School of Medicine, Hospital Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
Rodríguez
Julián
J
Department of Pediatrics, IUOPA, School of Medicine, Hospital Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
D000138:Acidosis / Q000503:physiopathology; D000643:Ammonium Chloride; D000704:Analysis of Variance; D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D019902:Chondrocytes / Q000473:pathology / Q000502:physiology; D005260:Female; D006130:Growth Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D006132:Growth Plate / Q000473:pathology / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D000643:Ammonium Chloride