Non-apoptotic functions of caspase-7 during osteogenesis

Abstract

Caspase-3 and -7 are generally known for their central role in the execution of apoptosis. However, their function is not limited to apoptosis and under specific conditions activation has been linked to proliferation or differentiation of specialised cell types. In the present study, we followed the localisation of the activated form of caspase-7 during intramembranous (alveolar and mandibular bones) and endochondral (long bones of limbs) ossification in mice. In both bone types, the activated form of caspase-7 was detected from the beginning of ossification during embryonic development and persisted postnatally. The bone status was investigated by microCT in both wild-type and caspase-7-deficient adult mice. Intramembranous bone in mutant mice displayed a statistically significant decrease in volume while the mineral density was not altered. Conversely, endochondral bone showed constant volume but a significant decrease in mineral density in caspase-7 knock-out mice. Cleaved caspase-7 was present in a number of cells that did not show signs of apoptosis. PCR array analysis of the mandibular bone of caspase-7-deficient versus wild-type mice pointed to a significant decrease in mRNA levels for Msx1 and Smad1 in early bone formation. These observations might explain the decrease in the alveolar bone volume of adult knock-out mice. In conclusion, this study is the first to report a non-apoptotic function of caspase-7 in osteogenesis and also demonstrates further specificities in endochondral versus intramembranous ossification.

Apoptotic and nonapoptotic function of caspase 7 in spermatogenesis

“…While normal spermatogenesis is persistently impaired and spermatogenic cells are mostly disappeared, caspase 7 expression in Leydig cells may be activated by caspase 3, caspase 6, and caspase 9 to induce apoptosis. Thus, these findings suggest that the location of caspase 7 may impact on its function, which is similar with the recent reports 131415. However, whether the cleaved form of caspase 7 in germ cells is inevitable during normal spermatogenesis remains unclear.…”

“…The nonapoptotic functions of caspase 7 are found in tooth development, which play important roles in the differentiation of cells during odontogenesis 1314. Moreover, the activated form of caspase 7 is presented in a number of bone cells, but it is not in connection with apoptosis 15. Thus, these studies suggest that caspase 7 has an apoptotic and nonapoptotic function.…”

Apoptosis-associated protein expression in human salivary gland morphogenesis

“…Nuclear expression of executioner caspase-7 has been reported to indicate active apoptotic functions during osteogenesis of tooth and jaw development and within the primary enamel knot (Leist & Jäättelä, 2001;Matalova, Vanden Berghe, et al, 2012;Miura, 2012;Svandova et al, 2014). Similarly, our results demonstrated prevalent nuclear caspase-7 expression during ductal formation, especially near presumptive lumenal areas.…”

Dual Site Phosphorylation of Caspase-7 by PAK2 Blocks Apoptotic Activity by Two Distinct Mechanisms

“…The significance of this regulation could extend beyond cancer resistance and apoptotic activation. Recent discoveries have implicated caspase-7 in inflammation (Erener et al, 2012; Lamkanfi et al, 2008), defense against L. pneumophila infection (Akhter et al, 2009), osteogenesis (Svandova et al, 2014), and tooth development (Matalova et al, 2013), all of which show caspase-7 has distinct roles from caspase-3. These non-apoptotic roles could share regulation by phosphorylation and the mechanistic details uncovered here.…”