Department of Biodiversity Protection (DBP), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences (IAR&FR PAS), Olsztyn, Poland.
Department of Animal Biochemistry and Biotechnology, Faculty of Animal Bioengineering, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
PLoS One. 2023 Jul 10;18(7):e0287782. doi: 10.1371/journal.pone.0287782. eCollection 2023.
Metalloproteinases (MMP)s regulate developmental processes, control angiogenesis and wound healing, participate in the formation of immune receptors, and are expressed in stem cells. Retinoic acid (RA) is a potential modulator of these proteinases. The aim was to determine (1) MMPs' action in antler stem cells (ASCs) before and after differentiation into adipo-, osteo-, and chondrocytes and (2) the effect of RA on modifying MMP action in ASCs. Antler tissue from pedicle was collected approximately 40 days after antler casting, post mortem from healthy breeding five year old males (N = 7). The cells were isolated from the pedicle layer of periosteum after skin separation and cultured. The pluripotency of the ASCs was evaluated by mRNA expression for NANOG, SOX2, and OCT4. ASCs were stimulated with RA (100nM) and differentiated for 14 days. The MMP (1-3) and TIMP(1-3) (tissue inhibitor of MMPs) mRNA expression was determined in the ASCs, their concentrations in the ASCs and the medium after RA stimulation as well as profiles of mRNA expression for MMPs: 1-3 and TIMPs: 1-3 during differentiation of ASC to osteocytes, adipocytes and chondrocytes. RA increased MMP-3 and TIMP-3 mRNA expression and output (P < 0.05) and not influenced on MMP-1 and TIMP-1 mRNA expression and output in ASC (P > 0.05). Depending on differentiation of ASC to osteocytes, adipocytes or chondrocytes, MMPsand TIMPsexpression profile fluctuates for all studied proteases and its inhibitors. The studies demand continuation considering the role of proteases in stem cells physiology and differentiation. The results may be relevant for the study of cellular processes during the cancerogenesis of tumor stem cells.
金属蛋白酶 (MMPs) 调节发育过程，控制血管生成和伤口愈合，参与免疫受体的形成，并在干细胞中表达。视黄酸 (RA) 是这些蛋白酶的潜在调节剂。目的是确定 (1) MMPs 在鹿角干细胞 (ASCs) 分化为脂肪细胞、成骨细胞和软骨细胞前后的作用，以及 (2) RA 对修饰 ASCs 中 MMPs 作用的影响。大约在鹿角铸造后 40 天，从健康的五岁雄性繁殖用鹿的角柄中采集鹿角组织 (N = 7)。将皮肤分离后，从骨膜的角柄层中分离出细胞并进行培养。通过 NANOG、SOX2 和 OCT4 的 mRNA 表达评估 ASCs 的多能性。用 RA (100nM) 刺激 ASCs 并分化 14 天。在 RA 刺激后，测定 ASCs 中的 MMP (1-3) 和 TIMP(1-3)（基质金属蛋白酶抑制剂）mRNA 表达及其浓度，以及 MMPs：1-3 和 TIMPs：1-3 在 ASCs 向成骨细胞、脂肪细胞和软骨细胞分化过程中的 mRNA 表达谱。RA 增加了 MMP-3 和 TIMP-3 的 mRNA 表达和产量 (P < 0.05)，但对 ASC 中 MMP-1 和 TIMP-1 的 mRNA 表达和产量没有影响 (P > 0.05)。根据 ASCs 向成骨细胞、脂肪细胞或软骨细胞的分化，所有研究的蛋白酶及其抑制剂的 MMPs 和 TIMPs 的表达谱都有波动。这些研究需要继续进行，以研究蛋白酶在干细胞生理学和分化中的作用。研究结果可能与研究肿瘤干细胞癌变过程中的细胞过程有关。
