**6. Current therapeutic measures for osteoporosis**

With recent advances in technology and knowledge, many therapeutic strategies are available for the management of osteoporosis (**Table 1**). Broadly, treatment measures against osteoporosis are classified under two classes: anti-resorptive and anabolic. Anti-resorptive agents work to reduce the rate of bone dissolution while anabolic agents attempt to boost bone formation and development.



**Table 1.**

*Different anti-osteoporotic therapeutic measures currently available in the market [56, 57].*

### **7. New therapeutic drug targets for osteoporosis**

Apart from tremendous progress in the therapeutic measures currently available for the check of osteoporosis, the disease still lacks complete eradication and immediate effective relief. The side effects, e.g., in bisphosphonate-based treatment, adverse effects like femoral fractures and jaw osteonecrosis, etc. are often observed. Moreover, instances of osteosarcoma are also reported in the anabolic therapies like parathyroid infusions [56, 58]. Hence, the hunt for the novel drugs that are specific in action is still continued. In the past few years, promising research on the topics related to functional genomics and system biology has emerged as a powerful remedial tool. Within this regard, RNAi (RNA interference) can serve as a new approach of therapeutics in combating bone associated injuries. miRNA-based gene antagonism is one such influential arena in the RNAi technology. miRNAs can interact well with genes or proteins involved in the process of osteogenic differentiation and mineralization.

#### **7.1 MicroRNAs (miRNAs)**

miRNAs, a category of small non-coding RNAs, are basically 21–23 nucleotides in length. They regulate the gene expression by interacting and degrading the complementary mRNA counterparts. Additionally, they also control the expression at the protein level via the mode of translational repression of the selected proteins. For the suppression of gene, miRNAs mediate mRNA degradation, mRNA decay, insulation in P bodies and mRNA deadenylation [59]. At the protein level, miRNAs act via inhibiting the initiation or elongation steps of the translation. miRNA might also cause ribosome drops and degradation of the nascent protein chain [59]. miRNAs were discovered in the year of 1990 as regulators of gene expression for the

**217**

**Figure 4.**

*at the protein level by translational repression.*

*MicroRNAs as Next Generation Therapeutics in Osteoporosis*

pri-miRNA (primary-miRNA) in the animals.

developmental processes in the Caenorhabditis elegans [60]. Interestingly, it has been stated that miRNA targets one-third of the genes in the human genome [61]. miRNAs are also found in extracellular fluids apart from the cells. Further, they are regarded as highly conserved elements among plant and animal kingdoms. In the context of nomenclature for the miRNAs, the preface "miR" is succeeded by a number that represents the order of naming, i.e. among miR-150 and miR-180, 150 represents the fact that it is discovered before 180 was found and named [62].

The miRNA synthesis can be briefly summarized in the following points

a.The miRNAs genes are generally transcribed by RNA Polymerase II as

c. Enzymes Drosha and Pasha present in a microprocessor complex cleave the long pri-miRNA to shorter pre-miRNA with 2 nucleotide overhangs at 3′ end

d. Finally, a nucleocytoplasmic shuttle protein viz. exportin translocates the

*Synthesis pathway for the miRNA. miRNA gene is synthesized by RNA polymerase II in the form of a primary transcript (Pri-miRNA). Pri-miRNA is acted upon by microprocessor complex (Drosha and Pasha) resulting in the formation of pre-miRNA. From the nucleus, pre-miRNA is transported to the cytoplasm by the shuttle protein exportin. In the cytoplasm, dicer targets the pre-miRNA and splices it to miRNA-miRNA duplex. The dicer cleavage is linked with the unwinding of the duplex and only one strand is selected to be incorporated into the RISC complex. In the RISC complex, miRNA executes its action either on mRNA via mRNA degradation or* 

b.A pri-miRNA may encompass one to seven miRNA precursors.

*DOI: http://dx.doi.org/10.5772/intechopen.91223*

**7.2 Biogenesis of miRNA**

and 5′ phosphates.

pre-miRNA to the cytoplasm.

(**Figure 4**) [63]:

developmental processes in the Caenorhabditis elegans [60]. Interestingly, it has been stated that miRNA targets one-third of the genes in the human genome [61]. miRNAs are also found in extracellular fluids apart from the cells. Further, they are regarded as highly conserved elements among plant and animal kingdoms. In the context of nomenclature for the miRNAs, the preface "miR" is succeeded by a number that represents the order of naming, i.e. among miR-150 and miR-180, 150 represents the fact that it is discovered before 180 was found and named [62].
