Somatostatin can locally inhibit proliferation and differentiation of cartilage and bone precursor cells

The influence of somatostatin on discrete stages of collagenous-matrix-induced endochondral bone formation has been investigated. Local injection of somatostatin, i.e., without any measurable systemic effect, resulted in a 75% reduction of cell proliferation as measured by [³H]thymidine incorporation and ornithine decarboxylase activities. The minimum effective inhibitory dose of somatostatin was 0.25 μg/day. Twice daily local injections of the hormone during cartilage formation also resulted in an inhibition, but this was shown to be due to impaired cell proliferation rather than to a direct effect of somatostatin on differentiation. Injection of somatostatin into developing bone tissue after the cartilage stage impaired osteogenesis, assessed by⁴⁵Ca incorporation and alkaline phosphatase activity. Concurrent injections of insulin and somatostatin obliterated the inhibitory effect of the latter on cell proliferation. Somatostatin can locally regulate the proliferation and differentiation of chondroprogenitor and osteoprogenitor cells in vivo and may directly contribute to the regulation of bone growth by its ability to counteract the stimulatory effect of insulin.