Calcitonin has direct effects on3[H]-thymidine incorporation and alkaline phosphatase activity in human osteoblast-line cells

Abstract

Calcitonin had direct and dose-dependent actions on human osteoblast-line cells (in serum-free monolayer culture) to increase cell proliferation and alkaline phosphatase activity/mg cell protein. Salmon calcitonin increased (human osteosarcoma) SaOS-2 cell proliferation, as evidenced by dose-dependent increases in 3[H]-thymidine incorporation into DNA (e.g., 153% of control after 20 h exposure at 0.1 nM, P less than 0.01), and MTT (thyzolyl blue) reduction/deposition (e.g., 161% of control after 72 h exposure at 0.03 nM). Continuous exposure was not required to elicit these proliferative responses. These effects were not unique to salmon calcitonin or to SaOS-2 cells. Similar effects were seen with human calcitonin (but not heat-inactivated human calcitonin) and with (human osteosarcoma) TE-85 cells and human osteoblast-line cells prepared from femoral heads. In addition to effects on cell proliferation, calcitonin also increased alkaline phosphatase-specific activity in SaOS-2 cells (e.g., 180% of control after 72 h of exposure to 0.1 nM salmon calcitonin, P less than .005).

Calcitonin-Induced Effects on Amniotic Fluid-Derived Mesenchymal Stem Cells

“…In-vitro studies have indicated that CT can modulate the expression of markers of the osteoblastic phenotype, such as ALP activity and collagen synthesis, in cell lines derived from chick calvaria [59], in transformed murine calvaria cell lines [20,60,61], in human osteosarcoma cells [22], and in normal human bone cells [58]. In our cell models, nanomolar concentrations of CT induced dose-dependent increases in ALP activity in the osteodifferentiating medium at 4 days of incubation.…”

“…Although these signalling pathways have been demonstrated to be mediated by direct binding of the hormone CT to the CTR expressed by osteoclasts [28], the presence of the CTR in osteoblasts still remains unclear and controversial, as well as which signalling cascade is activated by CT [18,29]. It has been reported that there are CTR-mediated effects in osteoblastic cell lines and primary cultures of osteoblast-like cells of rodent [30][31][32], and human [22,29,33] origins; on the other hand, Naot and Cornish showed high levels of CTR-like receptor, but no expression of the CTR, in human primary osteoblasts [24]. The variability of the available data might be dependent on the complexity of the CT/CTR system, the variety of CT-family factors, the several patterns of receptor expression and assembly in cell lines, and the different experimental models used [24].…”

“…CT functions through limiting the number of osteoclasts and inhibiting their motility and secretory activity [16,17], and by inducing a burst of proliferation and functional activation of osteoblasts [18,19]. Farley and colleagues reported direct effects of CT on different osteoblastic cell models: i.e., murine bone cells [20], human osteosarcoma (SAOS-2, TE-85) cells, and normal human osteoblast-like cells isolated from the head of the femur [21,22]. CT has also been reported to prevent osteoblast and osteocyte apoptosis in murine cell lines and primary cultures of osteoblast-like cells, which appears to occur via actions mediated by receptors linked to the adenylyl cyclase system [23].…”

Femoral Neck Trabecular Microstructure in Ovariectomized Ewes Treated With Calcitonin: MRI Microscopic Evaluation

“…In addition to its inhibitory effects on osteoclastic bone resorption, calcitonin may enhance osteoblastic bone formation. (22,23) Studies in OVX rats using traditional 2D bone histomorphometry have shown that subcutaneous administration of calcitonin is associated with a partial inhibition of the OVX-induced increase in bone resorption, without detriment effects on osteoid volume or mineralization lag time. (24,25) In young adult rats, 3 U/kg subcutaneously for 40 days did not show detrimental effects on femoral torsional mechanical properties, (38) whereas adult beagles treated with calcitonin at 8 mg/kg/day for one-half of a year had a significant decrease in the whole lumber vertebra (L 2 ) strength.…”

“…(22,23) It inhibits OVX-induced increase of bone resorption in rats. (24,25) We have shown that salmon calcitonin (sCT) preserved BMD measured by DXA and bone strength in trabecular bone of the femoral neck in sheep treated with sCT.…”