The growth of newborn rat tibiae in a continuousflow organ culture system

Schwartz, Peter; Wettenhall, Richard E.H.; Börnstein, J.

doi:10.1002/jez.1401680412

Cited by 10 publications

(2 citation statements)

References 43 publications

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“…Studies toward this end from our laboratory have in the past relied predominantly on in vivo experiments (3,4). Although a large number of investigators have examined bone metabolism in vitro (5)(6)(7)(8)(9), none of these studies involved a chemically defined system in which simultaneously enhanced bone formation and resorption could be demonstrated. We have developed such an in vitro system and describe the details herein.…”

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confidence: 99%

Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism.

Howard¹,

Bottemiller²,

Turner³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

231

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We have developed an in vitro system, using embryonic chicken tibiae grown in a serum-free medium, which exhibits simultaneous bone formation and resorption. Tibiae from 8-day embryos increased in mean (±SD) length (4.0 ± 0.4 to 11.0 ± 0.3 mm) and dry weight (0.30 ± 0.04 to 0.84 ± 0.04 mg) during 12 days in vitro. There was increased incorporation of [3H]proline into hydroxyproline (120 ± 20 to 340 ± 20 cpm/mg of bone per 24 hr) as a measure of collagen synthesis, as well as a 62 ± 5% increase in total calcium and 45Ca taken up as an indication of active mineralization. A physiologic concentration (1 pM) of parathyroid hormone was found to stimulate bone resorption over control levels in this system. Parathyroid hormone stimulated the release of [3H]hydroxyproline from the bone shafts but not from the cartilage ends, indicating the specificity of theresponse. With 1 pM parathyroid hormone we observed an acute inhibition of bone formation, followed (after 12-16 hr) by a chronic stimulation of bone formation during the 12-day incubation. Both mineral uptake and matrix formation were enhanced at approximately the same rate during the 12-day incubation. The chronic enhancement of formation required parathyroid hormone only for the initial 8-10 hr of incubation. These results could be explained by the production or release ofa factor from bone to stimulate formation in response to the acute increase in resorption-a "coupling factor." Indeed, dialyzed culture medium conditioned by actively resorbing bones stimulated bone formation over controls when added to organ cultures at a 1:20 dilution. The factor is larger than 12,000 daltons as determined by dialysis. The factor is specific for the bone shaft and did not affect the cartilage ends. Work directed toward a better understanding of the regulation of bone metabolism has shown that bone formation and bone resorption are coupled in vivo (1). This coupling occurs even in some disease states (e.g., hyper-and hypoparathyroidism, Paget disease, and acromegaly) (2). Detailed knowledge of the regulatory mechanism of coupling could lead to better understanding of the problems of metabolic bone disease. Studies toward this end from our laboratory have in the past relied predominantly on in vivo experiments (3,4). Although a large number of investigators have examined bone metabolism in vitro (5-9), none of these studies involved a chemically defined system in which simultaneously enhanced bone formation and resorption could be demonstrated. We have developed such an in vitro system and describe the details herein.We have utilized this coupled system to study the effects of parathyroid hormone (PTH) on bone metabolism in vitro in an attempt to clarify what appears to be a disagreement in the literature concerning these effects. The acute effect in vivo is reported to be the stimulation of bone resorption and inhibition of bone formation (10,11). Chronic in vivo treatment of young growing rats with PTH results in an increase in formation and resorption (4) and a net ga...

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confidence: 99%

Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism.

Howard¹,

Bottemiller²,

Turner³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

231

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“…In 24-hour cultures, calvaria showed less resorption than in stationary culture. Short-term responses to PTH and calcitonin were similar to those observed in VIVO. J Dent Res 56 (8): 971-975 August 1977.…”

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confidence: 98%