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The Role of the Resting Zone in Growth Plate Chondrogenesis

Developmental Endocrinology Branch (V.A., J.L.M., M.W., R.I.G., K.M.B., J.B.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Department of Woman and Child Health (O.N.), Pediatric Endocrinology Unit Q2:08, Astrid Lindgren Children’s Hospital, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden; and Veterinary Resources Program (J.D.B.), Office of Research Services, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Jeffrey Baron, M.D., National Institutes of Health, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, Maryland 20892-1862. E-mail: . jeffrey_baron{at}nih.gov

In mammals, growth of long bones occurs at the growth plate, a cartilage structure that contains three principal layers: the resting, proliferative, and hypertrophic zones. The function of the resting zone is not well understood. We removed the proliferative and hypertrophic zones from the rabbit distal ulnar growth plate in vivo, leaving only the resting zone. Within 1 wk, a complete proliferative and hypertrophic zone often regenerated. Next, we manipulated growth plates in vivo to place resting zone cartilage ectopically alongside the proliferative columns. Ectopic resting zone cartilage induced a 90-degree shift in the orientation of nearby proliferative zone chondrocytes and seemed to inhibit their hypertrophic differentiation. Our findings suggest that resting zone cartilage makes important contributions to endochondral bone formation at the growth plate: 1) it contains stem-like cells that give rise to clones of proliferative chondrocytes; 2) it produces a growth plate-orienting factor, a morphogen, that directs the alignment of the proliferative clones into columns parallel to the long axis of the bone; and 3) it may also produce a morphogen that inhibits terminal differentiation of nearby proliferative zone chondrocytes and thus may be partially responsible for the organization of the growth plate into distinct zones of proliferation and hypertrophy.

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