**7.2 Biogenesis of miRNA**

*Clinical Implementation of Bone Regeneration and Maintenance*

**dose of the drug**

Denosumab 60 mg/ml It is a human monoclonal

Teriparatide 250 mcg/ml It is a recombinant part of

**Mechanism/effect Harmful effects**

Shortness of breathing cycle, warm skin with pus, pain while urinating, and

Heartbeat rate is increased, severe dizziness, allergies, itching and swelling of face, tongue, faintness, and

night sweats

osteosarcoma

vomiting

and spinning sensation

Light-headed sensation, flushing, nausea, and

antibody against RANKL that prevents the formation and maturation

PTH, that stimulates the osteoblastogenesis with augmented bone mineral

formation, reduces calcium levels in the plasma, increases net bone mass

of osteoclasts

density

Abaloparatide 2000 mcg/ml Same as Teriparatide Hypercalciuria, palpitations,

**Drug Administration** 

**3. RANKL antagonist**

**Anabolic strategies**

**Table 1.**

**1. Parathyroid hormone (PTH)**

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

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

**2. Calcitonin** 200 IU/ml Encourages bone

osteogenic differentiation and mineralization.

**7.1 MicroRNAs (miRNAs)**

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

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

**216**

The miRNA synthesis can be briefly summarized in the following points (**Figure 4**) [63]:


#### **Figure 4.**

*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 at the protein level by translational repression.*

